# gene_set_details

systematic_name: M9708
exact_source: GSE46242_3746_200_DN
source_species_code: MM
GEO_id: GSE46242
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in anergic CD4 [GeneID=920] Th1 cells: wildtype versus EGR2 [GeneID=1959] knockout.

description_full:
[cell repeats an earlier one in this file: 1455 characters]


systematic_name: M9716
exact_source: GSE46242_3748_200_UP
source_species_code: MM
GEO_id: GSE46242
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] Th1 cells with EGR2 [GeneID=1959] knockout: control versus anergic.

description_full:
[cell repeats an earlier one in this file: 1455 characters]


systematic_name: M9717
exact_source: GSE46242_3748_200_DN
source_species_code: MM
GEO_id: GSE46242
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] Th1 cells with EGR2 [GeneID=1959] knockout: control versus anergic.

description_full:
[cell repeats an earlier one in this file: 1455 characters]


description_brief: Genes down-regulated in CD4 [GeneID=920] SMARTA T cells: naïve versus Th1 memory.
systematic_name: M9718
exact_source: GSE43863_3730_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  CD4 T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for longlived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh lineage after antigen clearance. Using adoptive transfer of antigen-specific memory CD4+ subpopulations (based on CXCR5 and Ly6c expression)in the LCMV infection model, we found that there are distinct memory CD4+ T cell populations with commitment to the Tfh and Th1 lineages. Our conclusions are based on gene expression profiles, epigenetic studies and phenotypic and functional analysis. The gene expression profiles of virus-specific CD4 T cell subets at effector and memory stages is presented here.


systematic_name: M9720
exact_source: GSE43863_3729_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA T cells: naïve versus Ly6c low CXCR5- effector during acute infection of LCMV.

description_full:
  CD4 T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for longlived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh lineage after antigen clearance. Using adoptive transfer of antigen-specific memory CD4+ subpopulations (based on CXCR5 and Ly6c expression)in the LCMV infection model, we found that there are distinct memory CD4+ T cell populations with commitment to the Tfh and Th1 lineages. Our conclusions are based on gene expression profiles, epigenetic studies and phenotypic and functional analysis. The gene expression profiles of virus-specific CD4 T cell subets at effector and memory stages is presented here.


systematic_name: M9721
exact_source: GSE43863_3729_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA T cells: naïve versus Ly6c low CXCR5- effector during acute infection of LCMV.

description_full:
  CD4 T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for longlived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh lineage after antigen clearance. Using adoptive transfer of antigen-specific memory CD4+ subpopulations (based on CXCR5 and Ly6c expression)in the LCMV infection model, we found that there are distinct memory CD4+ T cell populations with commitment to the Tfh and Th1 lineages. Our conclusions are based on gene expression profiles, epigenetic studies and phenotypic and functional analysis. The gene expression profiles of virus-specific CD4 T cell subets at effector and memory stages is presented here.


systematic_name: M9725
exact_source: GSE43863_3727_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA T cells: naïve versus effector during acute infection of LCMV.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9727
exact_source: GSE43863_3727_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA T cells: naïve versus effector during acute infection of LCMV.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9730
exact_source: GSE43863_3728_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA T cells: naïve versus Ly6c+ CXCR5+ [GeneID=643] effector during acute infection of LCMV.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9732
exact_source: GSE43863_3728_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA T cells: naïve versus Ly6c+ CXCR5+ [GeneID=643] effector during acute infection of LCMV.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9733
exact_source: GSE43863_3735_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in Ly6c int CXCR5+ CD4 [GeneID=643;920] T cells: effector during acute infection of LCMV versus memory.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9736
exact_source: GSE43863_3737_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA memory T cells: Th1 versus Ly6c int CXCR5+ [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9738
exact_source: GSE43863_3731_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA T cells: naïve versus memory follicular helper (Tfh).

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9739
exact_source: GSE43863_3732_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA T cells: naïve versus Ly6c int CXCR5+ [GeneID=643] memory.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9741
exact_source: GSE43863_3732_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA T cells: naïve versus Ly6c int CXCR5+ [GeneID=643] memory.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9742
exact_source: GSE43863_3733_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in Th1 CD4 [GeneID=920] SMARTA T cells: effector during acute infection of LCMV versus memory.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9744
exact_source: GSE43863_3733_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in Th1 CD4 [GeneID=920] SMARTA T cells: effector during acute infection of LCMV versus memory.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9745
exact_source: GSE43863_3734_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in follicular helper CD4 [GeneID=920] SMARTA T cells (Tfh): effector during acute infection of LCMV versus memory.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9747
exact_source: GSE43863_3734_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in follicular helper CD4 [GeneID=920] SMARTA T cells (Tfh): effector during acute infection of LCMV versus memory.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9748
exact_source: GSE43863_3735_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in Ly6c int CXCR5+ CD4 [GeneID=643;920] T cells: effector during acute infection of LCMV versus memory.

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9749
exact_source: GSE43863_3742_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: follicular helper (Tfh) versus Ly6c int CXCR5+ [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9750
exact_source: GSE43863_3743_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: follicular helper (Tfh) versus Ly6c low CXCR5- [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9751
exact_source: GSE43863_3743_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: follicular helper (Tfh) versus Ly6c low CXCR5- [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9754
exact_source: GSE43863_3744_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: Ly6c int CXCR5+ [GeneID=643] versus Ly6c low CXCR5- [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9755
exact_source: GSE43863_3744_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: Ly6c int CXCR5+ [GeneID=643] versus Ly6c low CXCR5- [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9757
exact_source: GSE43863_3737_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA memory T cells: Th1 versus Ly6c int CXCR5+ [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9759
exact_source: GSE43863_3738_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA memory T cells: follicular helper (Tfh) versus Ly6c int CXCR5+ [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9761
exact_source: GSE43863_3738_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA memory T cells: follicular helper (Tfh) versus Ly6c int CXCR5+ [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9762
exact_source: GSE43863_3739_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: Th1 versus follicular helper (Tfh).

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9763
exact_source: GSE43863_3739_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: Th1 versus follicular helper (Tfh).

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9764
exact_source: GSE43863_3740_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: Th1 versus Ly6c int CXCR5+ [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9765
exact_source: GSE43863_3740_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: Th1 versus Ly6c int CXCR5+ [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9767
exact_source: GSE43863_3741_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: Th1 versus Ly6c low CXCR5- [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9768
exact_source: GSE43863_3741_200_DN
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: Th1 versus Ly6c low CXCR5- [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9770
exact_source: GSE43863_3742_200_UP
source_species_code: MM
GEO_id: GSE43863
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] SMARTA effector T cells during acute infection of LCMV: follicular helper (Tfh) versus Ly6c int CXCR5+ [GeneID=643].

description_full:
[cell repeats an earlier one in this file: 751 characters]


systematic_name: M9771
exact_source: GSE46143_3799_200_UP
source_species_code: HS
GEO_id: GSE46143
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in MME+ [GeneID=4311] germinal center B lymphocytes: control versus over-expressing viral (EBV) gene LMP2A.

description_full:
  In this study, we have investigated the effect of LMP2A on gene expression in normal human GC B cells using a non-viral vector based system


systematic_name: M9773
exact_source: GSE46143_3799_200_DN
source_species_code: HS
GEO_id: GSE46143
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in MME+ [GeneID=4311] germinal center B lymphocytes: control versus over-expressing viral (EBV) gene LMP2A.

description_full:
  In this study, we have investigated the effect of LMP2A on gene expression in normal human GC B cells using a non-viral vector based system


description_brief: Genes up-regulated in CD8 T cells: resting versus activated.
systematic_name: M9774
exact_source: GSE44649_2406_200_UP
source_species_code: MM
GEO_id: GSE44649
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  MicroRNA-155 (miR-155) is upregulated in primary effector CD8 T cells but is expressed at low amounts in naïve cells. Anti-viral CD8 T cell responses and viral clearance were impaired in miR-155 deficient (bic-/-) mice, and this defect was intrinsic to CD8 T cells, as adoptively transferred bic-/- CD8 T cells generated greatly reduced primary and memory responses during infection. To understand the mechanism by which miR-155 regulates CD8 T cell activation, we analyzed the gene expression profiles of naive and in vitro activated wild-type and bic-/- CD8 T cells.


description_brief: Genes up-regulated in B lymphocytes: memory versus plasmablasts.
systematic_name: M9786
exact_source: GSE42724_3699_200_UP
source_species_code: HS
GEO_id: GSE42724
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  The recent discovery of the human B1 cells, identified by the expression of CD20, CD27 and CD43 in absence of expression of CD70 and CD69 has been subject of debate. Some studies have raised the possibility that these cells are B cells differentiating towards the plasmablast and plasma cell stage rather than being the human counterpart of murine B1 cells. No further in depth studies have been performed. Therefore, a functional comparison was made between, the proposed B1 cells and plasmablasts. We observed that for several functional characteristics (distribution of isotypes of spontaneously producted antibodies, production of antigen-specific antibodies after vaccination with both T-cell dependent as well as T-cell independent antigen, the proposed B1 cells behaved similar to plasmablasts. In addition, we were able to differentiate the proposed B1 cells in vitro, indicating that they are not from a distinct lineage as the murine B1 cells. Gene expression analysis revealed that these cells cluster between memory B cells and plasmablasts, contradicting them being the genuine human counterpart of murine B1 cells, rather revealing a preplasmablast phenotype.


description_brief: Genes up-regulated in macrophages: untreated versus TGFB2 [GeneID=7042].
systematic_name: M9803
exact_source: GSE45382_3797_200_UP
source_species_code: MM
GEO_id: GSE45382
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  F4/80+ macrophages treated with TGFb2 are potently tolerogenic. Our understanding of the molecular mechanisms mediating the development of these tolerogenic properties is incomplete. We used microarray analysis to identify molecules that are involved in the tolerogenic mechanisms in murine TGFb-treated macrophages.


systematic_name: M9807
exact_source: GSE46606_3705_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4-KO.

description_full:
  Temporal analysis of B cell activation in vitro using CD40L and IL-2/4/5 cytokines in wild type Irf4+/+ B cells or in mutant Irf4-/- B cells harboring a tet-inducible allele of Irf4. IRF4 expression was restored, or not, in the Irf4-/- background by culturing in the presence of low or high concentrations of doxycycline. The results provide insight in the role of IRF4 expression levels in coordinating different programs of B cell differentiation.


systematic_name: M9808
exact_source: GSE46606_3705_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4-KO.

description_full:
  Temporal analysis of B cell activation in vitro using CD40L and IL-2/4/5 cytokines in wild type Irf4+/+ B cells or in mutant Irf4-/- B cells harboring a tet-inducible allele of Irf4. IRF4 expression was restored, or not, in the Irf4-/- background by culturing in the presence of low or high concentrations of doxycycline. The results provide insight in the role of IRF4 expression levels in coordinating different programs of B cell differentiation.


systematic_name: M9812
exact_source: GSE46606_3706_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4-KO.

description_full:
  Temporal analysis of B cell activation in vitro using CD40L and IL-2/4/5 cytokines in wild type Irf4+/+ B cells or in mutant Irf4-/- B cells harboring a tet-inducible allele of Irf4. IRF4 expression was restored, or not, in the Irf4-/- background by culturing in the presence of low or high concentrations of doxycycline. The results provide insight in the role of IRF4 expression levels in coordinating different programs of B cell differentiation.


systematic_name: M9813
exact_source: GSE46606_3706_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4-KO.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9817
exact_source: GSE46606_3707_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9819
exact_source: GSE46606_3707_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9821
exact_source: GSE46606_3708_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9824
exact_source: GSE46606_3708_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9825
exact_source: GSE46606_3709_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4-KO.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9827
exact_source: GSE46606_3709_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4-KO.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9829
exact_source: GSE46606_3710_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4high.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9830
exact_source: GSE46606_3710_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4high.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9831
exact_source: GSE46606_3711_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4high.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9832
exact_source: GSE46606_3711_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4high.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9833
exact_source: GSE46606_3712_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4intermediate.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9835
exact_source: GSE46606_3712_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4intermediate.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9836
exact_source: GSE46606_3713_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4intermediate.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9837
exact_source: GSE46606_3713_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in at day 0 B cell IRF4-KO versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4intermediate.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9838
exact_source: GSE46606_3714_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4high versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4high.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9839
exact_source: GSE46606_3714_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4high versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4high.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9840
exact_source: GSE46606_3715_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4intermediate versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4intermediate.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9842
exact_source: GSE46606_3715_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4intermediate versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4intermediate.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9843
exact_source: GSE46606_3716_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4high versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4intermediate.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9844
exact_source: GSE46606_3716_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4high versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4intermediate.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9845
exact_source: GSE46606_3717_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4high versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4intermediate.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9846
exact_source: GSE46606_3717_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4high versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4intermediate.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9847
exact_source: GSE46606_3718_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4high versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9848
exact_source: GSE46606_3718_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4high versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9850
exact_source: GSE46606_3719_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4intermediate versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9851
exact_source: GSE46606_3719_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell IRF4intermediate versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9853
exact_source: GSE46606_3720_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4high versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9854
exact_source: GSE46606_3720_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4high versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9856
exact_source: GSE46606_3721_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4intermediate versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9859
exact_source: GSE46606_3721_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell IRF4intermediate versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9862
exact_source: GSE46606_3723_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in at day 0 B cell wildtype versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9864
exact_source: GSE46606_3723_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in at day 0 B cell wildtype versus CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9867
exact_source: GSE46606_3724_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in at day 0 B cell wildtype versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9870
exact_source: GSE46606_3724_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in at day 0 B cell wildtype versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9871
exact_source: GSE46606_3725_200_UP
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell wildtype versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9872
exact_source: GSE46606_3725_200_DN
source_species_code: MM
GEO_id: GSE46606
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD40L and IL-2 IL-4 IL-5 stimulated at day 1 B cell wildtype versus CD40L and IL-2 IL-4 IL-5 stimulated at day 3 B cell wildtype.

description_full:
[cell repeats an earlier one in this file: 449 characters]


systematic_name: M9873
exact_source: GSE46025_3672_200_UP
source_species_code: MM
GEO_id: GSE46025
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated during acute viral infection in KLRG1 low [GeneID=10219] CD8 T cells: wildtype versus FOXO1 [GeneID=2308] knockout.

description_full:
  The forkhead O transcription factors (FOXO) integrate a range of extracellular signals including growth factor signaling, inflammation, oxidative stress and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many cell-type specific responses yet to be unraveled. Naive antigen-specific CD8+ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure, but in addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival. We used microarrays to determine whether FOXO1 broadly affects effector and memory differentiation, and to what extent FOXO1 determines the program of memory T cell gene expression.


systematic_name: M9876
exact_source: GSE46025_3672_200_DN
source_species_code: MM
GEO_id: GSE46025
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated during acute viral infection in KLRG1 low [GeneID=10219] CD8 T cells: wildtype versus FOXO1 [GeneID=2308] knockout.

description_full:
  The forkhead O transcription factors (FOXO) integrate a range of extracellular signals including growth factor signaling, inflammation, oxidative stress and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many cell-type specific responses yet to be unraveled. Naive antigen-specific CD8+ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure, but in addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival. We used microarrays to determine whether FOXO1 broadly affects effector and memory differentiation, and to what extent FOXO1 determines the program of memory T cell gene expression.


description_brief: Genes up-regulated in CD4 [GeneID=920] T cells: NRAS [GeneID=4893] knockout versus wildtype.
systematic_name: M9877
exact_source: GSE45739_3749_200_UP
source_species_code: MM
GEO_id: GSE45739
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  It has been recently shown that N-ras plays a preferential role in immune cell development and function; specifically: N-ras, but not H-ras or K-ras, could be activated at and signal from the Golgi membrane of immune cells following a low level TCR stimulus. The goal of our studies was to test the hypothesis that N-ras and H-ras played distinct roles in immune cells at the level of the transcriptome. First, we showed via mRNA expression profiling that there were over four hundred genes that were uniquely differentially regulated either by N-ras or H-ras, which provided strong evidence in favor of the hypothesis that N-ras and H-ras have distinct functions in immune cells. We next characterized the genes that were differentially regulated by N-ras in T cells following a low-level TCR stimulus. Of the large pool of candidate genes that were differentially regulated by N-ras downstream of TCR ligation, four genes were verified in qRT-PCR-based validation experiments as being differentially regulated by N-ras (Dntt, Slc9a6, Chst1, and Lars2). Finally, although there was little overlap between individual genes that were regulated by N-ras in unstimulated thymocytes and stimulated CD4+ T-cells, there was a nearly complete correspondence between the signaling pathways that were regulated by N-ras in these two immune cell types. Since we were interested primarily in genes that were differentially regulated by N-ras following a low-level TCR stimulus, our microarray data comparison was between data from TCR-stimulated, WT CD4+ T-cells and from TCR-stimulated, N-ras KO CD4+ T-cells. Genes that were differentially regulated in the comparison between stimulated N-ras KO CD4+ T-cells and unstimulated N-ras KO CD4+ T-cells, as well as those genes that were differentially regulated in the comparison between stimulated WT CD4+ T-cells and unstimulated WT CD4+ T-cells were excluded from this analysis. To determine if N-ras and H-ras regulate different sets of genes in thymocytes, a comparison was made between the set of genes that were differentially regulated by N-ras in the [WT] vs. [N-ras KO] comparison and the set of genes that were differentially regulated by H-ras in the [WT] vs. [H-ras KO] comparison.


systematic_name: M9881
exact_source: GSE45739_3750_200_UP
source_species_code: MM
GEO_id: GSE45739
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in activated CD4 [GeneID=920] T cells: NRAS [GeneID=4893] knockout versus wildtype.

description_full:
  It has been recently shown that N-ras plays a preferential role in immune cell development and function; specifically: N-ras, but not H-ras or K-ras, could be activated at and signal from the Golgi membrane of immune cells following a low level TCR stimulus. The goal of our studies was to test the hypothesis that N-ras and H-ras played distinct roles in immune cells at the level of the transcriptome. First, we showed via mRNA expression profiling that there were over four hundred genes that were uniquely differentially regulated either by N-ras or H-ras, which provided strong evidence in favor of the hypothesis that N-ras and H-ras have distinct functions in immune cells. We next characterized the genes that were differentially regulated by N-ras in T cells following a low-level TCR stimulus. Of the large pool of candidate genes that were differentially regulated by N-ras downstream of TCR ligation, four genes were verified in qRT-PCR-based validation experiments as being differentially regulated by N-ras (Dntt, Slc9a6, Chst1, and Lars2). Finally, although there was little overlap between individual genes that were regulated by N-ras in unstimulated thymocytes and stimulated CD4+ T-cells, there was a nearly complete correspondence between the signaling pathways that were regulated by N-ras in these two immune cell types. Since we were interested primarily in genes that were differentially regulated by N-ras following a low-level TCR stimulus, our microarray data comparison was between data from TCR-stimulated, WT CD4+ T-cells and from TCR-stimulated, N-ras KO CD4+ T-cells. Genes that were differentially regulated in the comparison between stimulated N-ras KO CD4+ T-cells and unstimulated N-ras KO CD4+ T-cells, as well as those genes that were differentially regulated in the comparison between stimulated WT CD4+ T-cells and unstimulated WT CD4+ T-cells were excluded from this analysis. To determine if N-ras and H-ras regulate different sets of genes in thymocytes, a comparison was made between the set of genes that were differentially regulated by N-ras in the [WT] vs. [N-ras KO] comparison and the set of genes that were differentially regulated by H-ras in the [WT] vs. [H-ras KO] comparison.


systematic_name: M9882
exact_source: GSE45739_3750_200_DN
source_species_code: MM
GEO_id: GSE45739
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in activated CD4 [GeneID=920] T cells: NRAS [GeneID=4893] knockout versus wildtype.

description_full:
[cell repeats an earlier one in this file: 2230 characters]


systematic_name: M9883
exact_source: GSE45739_3751_200_UP
source_species_code: MM
GEO_id: GSE45739
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD4 [GeneID=920] T cells with NRAS [GeneID=4893] knockout: unstimulated versus activated.

description_full:
[cell repeats an earlier one in this file: 2230 characters]


systematic_name: M9885
exact_source: GSE45739_3751_200_DN
source_species_code: MM
GEO_id: GSE45739
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD4 [GeneID=920] T cells with NRAS [GeneID=4893] knockout: unstimulated versus activated.

description_full:
[cell repeats an earlier one in this file: 2230 characters]


description_brief: Genes up-regulated in colonic lamina propria cells sorted by CXCR6 [GeneID=10663]: high versus low.
systematic_name: M9889
exact_source: GSE45881_3796_200_UP
source_species_code: MM
GEO_id: GSE45881
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  To identify the role of chemokine receptor in inflammation of colon, we isolated CD3+CD4+ helper T cells harboring CXCR6 from colonic lamina propria of mice We used microarrays to identify the differentially expressed genes between CXCR6Hi Tcells and CXCR6Lo Tcells


systematic_name: M9890
exact_source: GSE45881_3796_200_DN
source_species_code: MM
GEO_id: GSE45881
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in colonic lamina propria cells sorted by CXCR6 [GeneID=10663]: high versus low.

description_full:
  To identify the role of chemokine receptor in inflammation of colon, we isolated CD3+CD4+ helper T cells harboring CXCR6 from colonic lamina propria of mice We used microarrays to identify the differentially expressed genes between CXCR6Hi Tcells and CXCR6Lo Tcells


description_brief: Genes up-regulated in plasmacytoid dendritic cells: wildtype versus GFI1 [GeneID=2672] knockout.
systematic_name: M9892
exact_source: GSE45837_3674_200_UP
source_species_code: MM
GEO_id: GSE45837
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  Growth factor independence genes (Gfi1 and Gfi1b) repress recombination activating genes (Rag) transcription in developing B lymphocytes. Because all blood lineages originate from hematopoietic stem cells (HSCs) and different lineage progenitors have been shown to share transcription factor networks prior to cell fate commitment, we hypothesized that GFI family proteins may also play a role in repressing Rag transcription or a global lymphoid transcriptional program in other blood lineages. We tested the level of Rag transcription in various blood cells when Gfi1 and Gfi1b were deleted, and observed an upregulation of Rag expression in plasmacytoid dendritic cells (pDCs). Using microarray analysis, we observed that Gfi1 and Gfi1b regulate a broad spectrum of cellular processes in pDCs, but not a lymphoid specific transcriptional program. This study establishes a role for Gfi1 and Gfi1b in Rag regulation in a non-B lineage cell type


description_brief: Genes up-regulated in dendritic cells: untreated versus 24h after infection of Leishmania major.
systematic_name: M9895
exact_source: GSE42088_3826_200_UP
source_species_code: HS
GEO_id: GSE42088
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  Leishmania major infected human dendritic cells (DCs) exhibit a marked induction of IL-12 ultimately promoting a robust Th1-mediated response associated with parasite killing and protective immunity. In this study, we utilized Affymetrix Genechips to globally assess the host cell genes and pathways associated with L. major infection during early infection (2, 4, 8, and 24 hrs) in human myeloid-derived DCs. Bioinformatic analyses of the hybridized microarray chips identified 728 genes, represented by 848 unique probe sets, which, when compared to uninfected samples were observed to be significantly differentially expressed by one-way ANOVA. Altogether, the data provide a genome-wide perspective on the transcriptional influences Leishmania species exert within human DCs during early infection, and provides a platform for further investigations toward functionally characterizing candidate genes of importance to the IL-12 based immune response to infections. In the current study, we further investigate the L. major infected DC transcriptional during early time points after infection via microarray analysis.


description_brief: Genes down-regulated in B lymphocytes: untreated versus anti-IgM for 1h.
systematic_name: M9913
exact_source: GSE41176_3675_200_DN
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  The activation signaling of transcription factor nuclear factor-kB (NF-kB) plays central role for immune system. One of key kinase mediating this pathway is TAK1 in adaptive and innate immunity. However, role of TAK1 in B cell receptor signaling is still unclear. To know effects of TAK1-deletion on the gene expression induced by anti-IgM, we performed the time course analysis in comparison of wild type with TAK1-deleted splenic B cells.


systematic_name: M9918
exact_source: GSE41176_3682_200_UP
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in B lymphocytes with MAP3K7 [GeneID=6885] knockout: untreated versus anti IgM for 24h.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9920
exact_source: GSE41176_3682_200_DN
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in B lymphocytes with MAP3K7 [GeneID=6885] knockout: untreated versus anti IgM for 24h.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9926
exact_source: GSE41176_3679_200_UP
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in B lymphocytes with MAP3K7 [GeneID=6885] knockout: untreated versus anti IgM for 1h.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9928
exact_source: GSE41176_3679_200_DN
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in B lymphocytes with MAP3K7 [GeneID=6885] knockout: untreated versus anti IgM for 1h.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9929
exact_source: GSE41176_3680_200_UP
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in B lymphocytes with MAP3K7 [GeneID=6885] knockout: untreated versus anti IgM for 3h.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9930
exact_source: GSE41176_3680_200_DN
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in B lymphocytes with MAP3K7 [GeneID=6885] knockout: untreated versus anti IgM for 3h.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9931
exact_source: GSE41176_3681_200_UP
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in B lymphocytes with MAP3K7 [GeneID=6885] knockout: untreated versus anti IgM for 6h.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9933
exact_source: GSE41176_3681_200_DN
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in B lymphocytes with MAP3K7 [GeneID=6885] knockout: untreated versus anti IgM for 6h.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9934
exact_source: GSE41176_3684_200_UP
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in B lymphocytes treated by anti IgM for 1h: wildtype versus MAP3K7 [GeneID=6885] knockout.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9935
exact_source: GSE41176_3684_200_DN
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in B lymphocytes treated by anti IgM for 1h: wildtype versus MAP3K7 [GeneID=6885] knockout.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9938
exact_source: GSE41176_3685_200_UP
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in B lymphocytes treated by anti IgM for 3h: wildtype versus MAP3K7 [GeneID=6885] knockout.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9942
exact_source: GSE41176_3686_200_UP
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in B lymphocytes treated by anti IgM for 6h: wildtype versus MAP3K7 [GeneID=6885] knockout.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9943
exact_source: GSE41176_3686_200_DN
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in B lymphocytes treated by anti IgM for 6h: wildtype versus MAP3K7 [GeneID=6885] knockout.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9944
exact_source: GSE41176_3687_200_UP
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in B lymphocytes treated by anti IgM for 24h: wildtype versus MAP3K7 [GeneID=6885] knockout.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9950
exact_source: GSE41176_3685_200_DN
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in B lymphocytes treated by anti IgM for 3h: wildtype versus MAP3K7 [GeneID=6885] knockout.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9952
exact_source: GSE41176_3687_200_DN
source_species_code: MM
GEO_id: GSE41176
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in B lymphocytes treated by anti IgM for 24h: wildtype versus MAP3K7 [GeneID=6885] knockout.

description_full:
[cell repeats an earlier one in this file: 440 characters]


systematic_name: M9953
exact_source: GSE43260_3423_200_UP
source_species_code: HS
GEO_id: GSE43260
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in tumor-infiltrating CD8 T cells: BTLA+ [GeneID=151888] versus BTLA- [GeneID=151888].

description_full:
  Adoptive T-cell Therapy (ACT) involves using tumor-infiltrating lymphocytes (TIL) isolated from metastatic melanoma and expanding them ex vivo prior to infusion into lympho-depleted patients. This is one of the most promising approaches to treat metastatic melanoma, with the rates of clinical response between 48-50% based on studies done at NCI, M.D. Anderson Cancer Center (Houston, TX), and Sheba Medical Center (Tel Aviv, Israel). In the Phase II ACT Trial at M.D. Anderson Cancer Center , our group has uncovered an association between positive clinical response and the amount of CD8+ tumor-infiltrating lymphocytes expressing B and T Lymphocyte Attenuator (BTLA), a reported inhibitory receptor on T-cells. We used microarrays to detail the differences in the global programme of gene expression between CD8+BTLA+ vs CD8+BTLA- TILs in order to understand the molecular basis of the clinical association.


systematic_name: M9954
exact_source: GSE43260_3423_200_DN
source_species_code: HS
GEO_id: GSE43260
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in tumor-infiltrating CD8 T cells: BTLA+ [GeneID=151888] versus BTLA- [GeneID=151888].

description_full:
  Adoptive T-cell Therapy (ACT) involves using tumor-infiltrating lymphocytes (TIL) isolated from metastatic melanoma and expanding them ex vivo prior to infusion into lympho-depleted patients. This is one of the most promising approaches to treat metastatic melanoma, with the rates of clinical response between 48-50% based on studies done at NCI, M.D. Anderson Cancer Center (Houston, TX), and Sheba Medical Center (Tel Aviv, Israel). In the Phase II ACT Trial at M.D. Anderson Cancer Center , our group has uncovered an association between positive clinical response and the amount of CD8+ tumor-infiltrating lymphocytes expressing B and T Lymphocyte Attenuator (BTLA), a reported inhibitory receptor on T-cells. We used microarrays to detail the differences in the global programme of gene expression between CD8+BTLA+ vs CD8+BTLA- TILs in order to understand the molecular basis of the clinical association.


systematic_name: M9956
exact_source: GSE45365_3759_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated during primary acute viral infection: NK cells versus ITGAM+ [GeneID=3684] dendritic cells.

description_full:
  Murine Cytomegalovirus (MCMV) infection leads to early activation of various immune cells, including B and T lymphocytes, before the actual initiation of antigen-specific adaptive immunity. This activation is partly driven by innate cytokines, including type I interferon (IFN), which are induced early after infection. The objective of this study was to address the role of type I IFN in shaping early/innate B and T cell responses to a primary acute viral infection. In order to decipher the specific impact of IFN-I on cell subsets, we performed a genome-wide expression analysis on WT splenic B and CD8 T lymphocytes isolated from C57BL/6 [CD45.1 WT / CD45.2 IFNAR-KO] mixed bone marrow chimera mice. This study complements series GSE39555, which focused on early responses of NK cells and of the two subsets of conventional dendritic cells.


systematic_name: M9957
exact_source: GSE45365_3759_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated during primary acute viral infection: NK cells versus ITGAM+ [GeneID=3684] dendritic cells.

description_full:
  Murine Cytomegalovirus (MCMV) infection leads to early activation of various immune cells, including B and T lymphocytes, before the actual initiation of antigen-specific adaptive immunity. This activation is partly driven by innate cytokines, including type I interferon (IFN), which are induced early after infection. The objective of this study was to address the role of type I IFN in shaping early/innate B and T cell responses to a primary acute viral infection. In order to decipher the specific impact of IFN-I on cell subsets, we performed a genome-wide expression analysis on WT splenic B and CD8 T lymphocytes isolated from C57BL/6 [CD45.1 WT / CD45.2 IFNAR-KO] mixed bone marrow chimera mice. This study complements series GSE39555, which focused on early responses of NK cells and of the two subsets of conventional dendritic cells.


systematic_name: M9962
exact_source: GSE45365_3762_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD8A [GeneID=925] dendritic cells: wildtype versus IFNAR1 [GeneID=3454] knockout.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9963
exact_source: GSE45365_3762_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD8A [GeneID=925] dendritic cells: wildtype versus IFNAR1 [GeneID=3454] knockout.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9964
exact_source: GSE45365_3763_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated during primary acute viral infection in CD8A [GeneID=925] dendritic cells: wildtype versus IFNAR1 [GeneID=3454] knockout.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9966
exact_source: GSE45365_3763_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated during primary acute viral infection in CD8A [GeneID=925] dendritic cells: wildtype versus IFNAR1 [GeneID=3454] knockout.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9967
exact_source: GSE45365_3764_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD8A [GeneID=925] dendritic cells: control versus primary acute viral infection.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9968
exact_source: GSE45365_3764_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD8A [GeneID=925] dendritic cells: control versus primary acute viral infection.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9969
exact_source: GSE45365_3765_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in CD8A [GeneID=925] dendritic cells with IFNAR1 [GeneID=3454] knockout: control versus primary acute viral infection.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9970
exact_source: GSE45365_3765_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in CD8A [GeneID=925] dendritic cells with IFNAR1 [GeneID=3454] knockout: control versus primary acute viral infection.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9975
exact_source: GSE45365_3767_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated during primary acute viral infection in ITGAM+ [GeneID=3684] dendritic cells: wildtype versus IFNAR1 [GeneID=3454] knockout.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9977
exact_source: GSE45365_3767_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated during primary acute viral infection in ITGAM+ [GeneID=3684] dendritic cells: wildtype versus IFNAR1 [GeneID=3454] knockout.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9978
exact_source: GSE45365_3768_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in ITGAM+ [GeneID=3684] dendritic cells: control versus primary acute viral infection.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9979
exact_source: GSE45365_3768_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in ITGAM+ [GeneID=3684] dendritic cells: control versus primary acute viral infection.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9980
exact_source: GSE45365_3769_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in ITGAM+ [GeneID=3684] dendritic cells with IFNAR1 [GeneID=3454] knockout: control versus primary acute viral infection.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M9983
exact_source: GSE45365_3769_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in ITGAM+ [GeneID=3684] dendritic cells with IFNAR1 [GeneID=3454] knockout: control versus primary acute viral infection.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M10001
exact_source: GSE45365_3775_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in dendritic cells with IFNAR1 [GeneID=3454] knockout: CD8A [GeneID=925] versus ITGAM+ [GeneID=3684].

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M10002
exact_source: GSE45365_3775_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in dendritic cells with IFNAR1 [GeneID=3454] knockout: CD8A [GeneID=925] versus ITGAM+ [GeneID=3684].

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M10003
exact_source: GSE45365_3776_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated during primary acute viral infection in dendritic cells: CD8A [GeneID=925] versus ITGAM+ [GeneID=3684].

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M10004
exact_source: GSE45365_3776_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated during primary acute viral infection in dendritic cells: CD8A [GeneID=925] versus ITGAM+ [GeneID=3684].

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M10006
exact_source: GSE45365_3777_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated during primary acute viral infection in dendritic cells with IFNAR1 [GeneID=3454] knockout: CD8A [GeneID=925] versus ITGAM+ [GeneID=3684].

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M10007
exact_source: GSE45365_3777_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated during primary acute viral infection in dendritic cells with IFNAR1 [GeneID=3454] knockout: CD8A [GeneID=925] versus ITGAM+ [GeneID=3684].

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M10011
exact_source: GSE45365_3758_200_UP
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated during primary acute viral infection: NK cells versus CD8A [GeneID=625] dendritic cells.

description_full:
[cell repeats an earlier one in this file: 845 characters]


systematic_name: M10012
exact_source: GSE45365_3758_200_DN
source_species_code: MM
GEO_id: GSE45365
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated during primary acute viral infection: NK cells versus CD8A [GeneID=625] dendritic cells.

description_full:
[cell repeats an earlier one in this file: 845 characters]


description_brief: Genes down-regulated naïve CD4 [GeneID=920] T cells: Ly6c+ versus Ly6c-.
systematic_name: M10013
exact_source: GSE37336_3672_200_DN
source_species_code: MM
GEO_id: GSE37336
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  The naive CD4 T cell compartment is heterogeneous. Ly-6C- and Ly-6C+ Naive CD4 T cells were compare by microarrays.


description_brief: Genes up-regulated in macrophages: control versus glioblastoma conditioned.
systematic_name: M10014
exact_source: GSE18804_3830_200_UP
source_species_code: MM
GEO_id: GSE18804
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_full:
  Active immunotherapy is a promising strategy for anti-angiogenic cancer therapy. Recently, we have reported that a vaccine using human umbilical vein endothelial cells (HUVECs) induced specific anti-endothelial immune responses in the most of immunized patients, and resulted in tumor regression in some patients with recurrent malignant brain tumors, whereas not in colorectal cancer patients. In this study, we hypothesized that non-hypoxic perivascular tumor associated macrophages (TAMs) in colorectal cancer, but not in glioblastoma, might negatively alter the therapeutic efficacy of anti-angiogenic active immunotherapy. To test this hypothesis, we examined global gene expression profiles of non-hypoxic macrophages stimulated in vitro by soluble factors released from tumor cells of human glioblastoma U-87MG (‘brain TAMs’) or colorectal adenocarcinoma HT-29 (‘colon TAMs’).


systematic_name: M10017
exact_source: GSE18804_3833_200_DN
source_species_code: MM
GEO_id: GSE18804
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes down-regulated in tumor associated macrophages conditioned by: glioblastoma versus colorectal adenocarcinoma.

description_full:
  Active immunotherapy is a promising strategy for anti-angiogenic cancer therapy. Recently, we have reported that a vaccine using human umbilical vein endothelial cells (HUVECs) induced specific anti-endothelial immune responses in the most of immunized patients, and resulted in tumor regression in some patients with recurrent malignant brain tumors, whereas not in colorectal cancer patients. In this study, we hypothesized that non-hypoxic perivascular tumor associated macrophages (TAMs) in colorectal cancer, but not in glioblastoma, might negatively alter the therapeutic efficacy of anti-angiogenic active immunotherapy. To test this hypothesis, we examined global gene expression profiles of non-hypoxic macrophages stimulated in vitro by soluble factors released from tumor cells of human glioblastoma U-87MG (‘brain TAMs’) or colorectal adenocarcinoma HT-29 (‘colon TAMs’).


systematic_name: M10021
exact_source: GSE18804_3833_200_UP
source_species_code: MM
GEO_id: GSE18804
contributor: Jernej Godec
contrib_organization: Dana-Farber Cancer Institute
description_brief:
  Genes up-regulated in tumor associated macrophages conditioned by: glioblastoma versus colorectal adenocarcinoma.

description_full:
[cell repeats an earlier one in this file: 883 characters]


systematic_name: M40862
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/bin/NIHMS29119-supplement-sup_tbl1.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell (5 to 7)d vs 0d in adults (18-32) after exposure to APSV Wetvax , time point 5 to 7D

description_full:
  Gene expression in human peripheral blood mononuclear cells was systematically evaluated following smallpox and yellow fever vaccination, and naturally occurring upper respiratory infection (URI). All three infections were characterized by the induction of many interferon stimulated genes, as well as enhanced expression of genes involved in proteolysis and antigen presentation. Vaccinia infection was also characterized by a distinct expression signature composed of up-regulation of monocyte response genes, with repression of genes expressed by B and T-cells. In contrast, the yellow fever host response was characterized by a suppression of ribosomal and translation factors, distinguishing this infection from vaccinia and URI. No significant URI-specific signature was observed, perhaps reflecting greater heterogeneity in the study population and etiological agents. Taken together, these data suggest that specific host gene expression signatures may be identified that distinguish one or a small number of virus agents.


systematic_name: M40863
exact_source: Suppl Table 4a
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729923/#S1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood responders vs poor responders in adults (25-83) (responders) after exposure to Twinrix , time point 0D

description_full:
  Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear. In this study hepatitis B virus (HBV)-naive older adults received three vaccines, including one against HBV. Here we show, using transcriptional and cytometric profiling of whole blood collected before vaccination, that heightened expression of genes that augment B-cell responses and higher memory B-cell frequencies correlate with stronger responses to HBV vaccine. In contrast, higher levels of inflammatory response transcripts and increased frequencies of pro-inflammatory innate cells correlate with weaker responses to this vaccine. Increased numbers of erythrocytes and the haem-induced response also correlate with poor response to the HBV vaccine. A transcriptomics-based pre-vaccination predictor of response to HBV vaccine is built and validated in distinct sets of older adults. This moderately accurate (area under the curve ~65%) but robust signature is supported by flow cytometry and cytokine profiling. This study is the first that identifies baseline predictors and mechanisms of response to the HBV vaccine.


systematic_name: M40864
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528489/bin/1208972109_sd01.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 1d vs 0d in adults (20-50) after exposure to MRKAd5 HIV-1 gag/pol/nef , time point 1D. Comment: Table includes specific cell types

description_full:
  To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.


systematic_name: M40865
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/#SD1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 28d vs 0d in young adults (21-30) (responders) after exposure to Inactivated influenza vaccine , time point 28D

description_full:
  To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age >= 65) adults receiving influenza vaccine in two consecutive seasons and identified those with strong or absent response to vaccine, including a subset of older adults meeting criteria for frailty. PBMCs obtained prior to vaccination (Day 0) and at day 2 or 4, day 7 and day 28 post-vaccine were subjected to gene expression microarray analysis. We defined a response signature and also detected induction of a type I interferon response at day 2 and a plasma cell signature at day 7 post-vaccine in young responders. The response signature was dysregulated in older adults, with the plasma cell signature induced at day 2, and was never induced in frail subjects (who were all non-responders). We also identified a mitochondrial signature in young vaccine responders containing genes mediating mitochondrial biogenesis and oxidative phosphorylation that was consistent in two different vaccine seasons and verified by analyses of mitochondrial content and protein expression. These results represent the first genome-wide transcriptional profiling analysis of age-associated dynamics following influenza vaccination, and implicate changes in mitochondrial biogenesis and function as a critical factor in human vaccine responsiveness.


systematic_name: M40866
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/#SD1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 7d vs 0d in young adults (21-30) (responders) after exposure to Inactivated influenza vaccine , time point 7D. Comment: most (70-80%) of cohort were white

description_full:
  To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age >= 65) adults receiving influenza vaccine in two consecutive seasons and identified those with strong or absent response to vaccine, including a subset of older adults meeting criteria for frailty. PBMCs obtained prior to vaccination (Day 0) and at day 2 or 4, day 7 and day 28 post-vaccine were subjected to gene expression microarray analysis. We defined a response signature and also detected induction of a type I interferon response at day 2 and a plasma cell signature at day 7 post-vaccine in young responders. The response signature was dysregulated in older adults, with the plasma cell signature induced at day 2, and was never induced in frail subjects (who were all non-responders). We also identified a mitochondrial signature in young vaccine responders containing genes mediating mitochondrial biogenesis and oxidative phosphorylation that was consistent in two different vaccine seasons and verified by analyses of mitochondrial content and protein expression. These results represent the first genome-wide transcriptional profiling analysis of age-associated dynamics following influenza vaccination, and implicate changes in mitochondrial biogenesis and function as a critical factor in human vaccine responsiveness.


systematic_name: M40867
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/bin/aging-07-38-s002.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell young adults vs seniors in young adults (21-30), seniors (70+) after exposure to Inactivated influenza vaccine , time point 0D

description_full:
  To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age >= 65) adults receiving influenza vaccine in two consecutive seasons and identified those with strong or absent response to vaccine, including a subset of older adults meeting criteria for frailty. PBMCs obtained prior to vaccination (Day 0) and at day 2 or 4, day 7 and day 28 post-vaccine were subjected to gene expression microarray analysis. We defined a response signature and also detected induction of a type I interferon response at day 2 and a plasma cell signature at day 7 post-vaccine in young responders. The response signature was dysregulated in older adults, with the plasma cell signature induced at day 2, and was never induced in frail subjects (who were all non-responders). We also identified a mitochondrial signature in young vaccine responders containing genes mediating mitochondrial biogenesis and oxidative phosphorylation that was consistent in two different vaccine seasons and verified by analyses of mitochondrial content and protein expression. These results represent the first genome-wide transcriptional profiling analysis of age-associated dynamics following influenza vaccination, and implicate changes in mitochondrial biogenesis and function as a critical factor in human vaccine responsiveness.


systematic_name: M40868
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528489/bin/1208972109_sd01.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 1d vs 0d in adults (20-50) after exposure to MRKAd5 HIV-1 gag/pol/nef , time point 1D. Comment: Table includes specific cell types

description_full:
  To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.


systematic_name: M40869
exact_source: Suppl Table 4a
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729923/#S1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood responders vs poor responders in adults (25-83) (responders) after exposure to Twinrix , time point 0D

description_full:
  Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear. In this study hepatitis B virus (HBV)-naive older adults received three vaccines, including one against HBV. Here we show, using transcriptional and cytometric profiling of whole blood collected before vaccination, that heightened expression of genes that augment B-cell responses and higher memory B-cell frequencies correlate with stronger responses to HBV vaccine. In contrast, higher levels of inflammatory response transcripts and increased frequencies of pro-inflammatory innate cells correlate with weaker responses to this vaccine. Increased numbers of erythrocytes and the haem-induced response also correlate with poor response to the HBV vaccine. A transcriptomics-based pre-vaccination predictor of response to HBV vaccine is built and validated in distinct sets of older adults. This moderately accurate (area under the curve ~65%) but robust signature is supported by flow cytometry and cytokine profiling. This study is the first that identifies baseline predictors and mechanisms of response to the HBV vaccine.


systematic_name: M40870
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/#SD1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 28d vs 0d in young adults (21-30) (responders) after exposure to Inactivated influenza vaccine , time point 28D

description_full:
[cell repeats an earlier one in this file: 1385 characters]


systematic_name: M40871
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/#SD1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 7d vs 0d in young adults (21-30) (responders) after exposure to Inactivated influenza vaccine , time point 7D

description_full:
[cell repeats an earlier one in this file: 1385 characters]


systematic_name: M40872
exact_source: Suppl Table 11
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528489/bin/1208972109_sd01.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell Ad5 nAb titers >= 200Ad5 nAb titers <= 200 in adults (20-50) (Ad5 nAb titers > 200) after exposure to MRKAd5 HIV-1 gag/pol/nef , time point 1D. Comment: Impaired down-regulation. Genes with MRKAd5/HIV-induced expression responses significantly impacted by Ad5 nAbs (24hrs). Table includes specific cell types.

description_full:
  To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.


systematic_name: M40873
exact_source: Suppl Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072604/bin/ppat.1005892.s003.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with contraction of VZV specific T cells (peak to 28d) in peripheral blood mononuclear cell in seniors (50-75) after exposure to Zostavax , time point 1D

description_full:
  Vaccination with attenuated live varicella zoster virus (VZV) can prevent zoster reactivation, but protection is incomplete especially in an older population. To decipher the molecular mechanisms underlying variable vaccine responses, T- and B-cell responses to VZV vaccination were examined in individuals of different ages including identical twin pairs. Contrary to the induction of VZV-specific antibodies, antigen-specific T cell responses were significantly influenced by inherited factors. Diminished generation of long-lived memory T cells in older individuals was mainly caused by increased T cell loss after the peak response while the expansion of antigen-specific T cells was not affected by age. Gene expression in activated CD4 T cells at the time of the peak response identified gene modules related to cell cycle regulation and DNA repair that correlated with the contraction phase of the T cell response and consequently the generation of long-lived memory cells. These data identify cell cycle regulatory mechanisms as targets to reduce T cell attrition in a vaccine response and to improve the generation of antigen-specific T cell memory, in particular in an older population.


systematic_name: M40874
exact_source: Suppl Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072604/bin/ppat.1005892.s003.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with expansion of VZV specific T cells (0d to peak) in peripheral blood mononuclear cell in seniors (50-75) after exposure to Zostavax , time point 1D

description_full:
  Vaccination with attenuated live varicella zoster virus (VZV) can prevent zoster reactivation, but protection is incomplete especially in an older population. To decipher the molecular mechanisms underlying variable vaccine responses, T- and B-cell responses to VZV vaccination were examined in individuals of different ages including identical twin pairs. Contrary to the induction of VZV-specific antibodies, antigen-specific T cell responses were significantly influenced by inherited factors. Diminished generation of long-lived memory T cells in older individuals was mainly caused by increased T cell loss after the peak response while the expansion of antigen-specific T cells was not affected by age. Gene expression in activated CD4 T cells at the time of the peak response identified gene modules related to cell cycle regulation and DNA repair that correlated with the contraction phase of the T cell response and consequently the generation of long-lived memory cells. These data identify cell cycle regulatory mechanisms as targets to reduce T cell attrition in a vaccine response and to improve the generation of antigen-specific T cell memory, in particular in an older population.


systematic_name: M40875
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528489/bin/1208972109_sd01.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (20-50) after exposure to MRKAd5 HIV-1 gag/pol/nef , time point 3D. Comment: Table includes specific cell types

description_full:
[cell repeats an earlier one in this file: 1539 characters]


systematic_name: M40876
exact_source: Suppl Table 11
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528489/bin/1208972109_sd01.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell Ad5 nAb titers > 200 vs Ad5 nAb titers <= 200 in adults (20-50) (Ad5 nAb titers > 200) after exposure to MRKAd5 HIV-1 gag/pol/nef , time point 1D. Comment: Impaired up-regulation. Genes with MRKAd5/HIV-induced expression responses significantly impacted by Ad5 nAbs (24hrs). Table includes specific cell types.

description_full:
[cell repeats an earlier one in this file: 1539 characters]


systematic_name: M40877
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/bin/NIHMS29119-supplement-sup_tbl1.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell (50 to 60)d vs 0d in adults (18-32) after exposure to APSV Wetvax , time point 50 to 60D

description_full:
  Gene expression in human peripheral blood mononuclear cells was systematically evaluated following smallpox and yellow fever vaccination, and naturally occurring upper respiratory infection (URI). All three infections were characterized by the induction of many interferon stimulated genes, as well as enhanced expression of genes involved in proteolysis and antigen presentation. Vaccinia infection was also characterized by a distinct expression signature composed of up-regulation of monocyte response genes, with repression of genes expressed by B and T-cells. In contrast, the yellow fever host response was characterized by a suppression of ribosomal and translation factors, distinguishing this infection from vaccinia and URI. No significant URI-specific signature was observed, perhaps reflecting greater heterogeneity in the study population and etiological agents. Taken together, these data suggest that specific host gene expression signatures may be identified that distinguish one or a small number of virus agents.


systematic_name: M40878
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in T cell 3d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 3D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
  Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses.


systematic_name: M40879
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/bin/NIHMS29119-supplement-sup_tbl1.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell (5 to 7)d vs 0d in adults (18-32) after exposure to APSV Wetvax , time point 5 to 7D

description_full:
  Gene expression in human peripheral blood mononuclear cells was systematically evaluated following smallpox and yellow fever vaccination, and naturally occurring upper respiratory infection (URI). All three infections were characterized by the induction of many interferon stimulated genes, as well as enhanced expression of genes involved in proteolysis and antigen presentation. Vaccinia infection was also characterized by a distinct expression signature composed of up-regulation of monocyte response genes, with repression of genes expressed by B and T-cells. In contrast, the yellow fever host response was characterized by a suppression of ribosomal and translation factors, distinguishing this infection from vaccinia and URI. No significant URI-specific signature was observed, perhaps reflecting greater heterogeneity in the study population and etiological agents. Taken together, these data suggest that specific host gene expression signatures may be identified that distinguish one or a small number of virus agents.


systematic_name: M40880
exact_source: Suppl Table 9
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528489/bin/1208972109_sd01.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 1d vs 0d in adults (20-50) after exposure to MRKAd5 HIV-1 gag/pol/nef , time point 1D. Comment: Additional genes induced by MRKAd5 in vivo and in vitro, identified by exon-level analysis

description_full:
[cell repeats an earlier one in this file: 1539 characters]


systematic_name: M40881
exact_source: Suppl Table 14
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528489/bin/1208972109_sd01.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with CD8+ T-cell response in peripheral blood mononuclear cell in adults (20-50) after exposure to MRKAd5 HIV-1 gag/pol/nef , time point 3D

description_full:
[cell repeats an earlier one in this file: 1539 characters]


systematic_name: M40882
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/#SD1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 7d vs 0d in young adults (21-30) (nonresponder) after exposure to Inactivated influenza vaccine , time point 7D

description_full:
[cell repeats an earlier one in this file: 1385 characters]


systematic_name: M40883
exact_source: Fig 6
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 48h vs 0h in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 48H

description_full:
  The live vaccine strain (LVS) of Francisella tularensis is the only vaccine against tularemia available for humans, yet its mechanism of protection remains unclear. We probed human immunological responses to LVS vaccination with transcriptome analysis using PBMC samples from volunteers at time points pre- and post-vaccination. Gene modulation was highly uniform across all time points, implying commonality of vaccine responses. Principal components analysis revealed three highly distinct principal groupings: pre-vaccination (-144 h), early (+18 and +48 h), and late post-vaccination (+192 and +336 h). The most significant changes in gene expression occurred at early post-vaccination time points (<=48h), specifically in the induction of pro-inflammatory and innate immunity-related genes. Evidence supporting modulation of innate effector function, specifically antigen processing and presentation by dendritic cells, was especially apparent. Our data indicate that the LVS strain of F. tularensis invokes a strong early response upon vaccination. This pattern of gene regulation may provide insightful information regarding both vaccine efficacy and immunopathogenesis that may provide insight into infection with virulent strains of F. tularensis. Additionally, we obtained valuable information that should prove useful in evaluation of vaccine lots as well as efficacy testing of new anti-F. tularensis vaccines.


systematic_name: M40884
exact_source: Fig 6
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 18hr vs 0hr in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 18H

description_full:
  The live vaccine strain (LVS) of Francisella tularensis is the only vaccine against tularemia available for humans, yet its mechanism of protection remains unclear. We probed human immunological responses to LVS vaccination with transcriptome analysis using PBMC samples from volunteers at time points pre- and post-vaccination. Gene modulation was highly uniform across all time points, implying commonality of vaccine responses. Principal components analysis revealed three highly distinct principal groupings: pre-vaccination (-144 h), early (+18 and +48 h), and late post-vaccination (+192 and +336 h). The most significant changes in gene expression occurred at early post-vaccination time points (<=48h), specifically in the induction of pro-inflammatory and innate immunity-related genes. Evidence supporting modulation of innate effector function, specifically antigen processing and presentation by dendritic cells, was especially apparent. Our data indicate that the LVS strain of F. tularensis invokes a strong early response upon vaccination. This pattern of gene regulation may provide insightful information regarding both vaccine efficacy and immunopathogenesis that may provide insight into infection with virulent strains of F. tularensis. Additionally, we obtained valuable information that should prove useful in evaluation of vaccine lots as well as efficacy testing of new anti-F. tularensis vaccines.


systematic_name: M40885
exact_source: Fig 6
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 336h vs 0h in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 336H

description_full:
  The live vaccine strain (LVS) of Francisella tularensis is the only vaccine against tularemia available for humans, yet its mechanism of protection remains unclear. We probed human immunological responses to LVS vaccination with transcriptome analysis using PBMC samples from volunteers at time points pre- and post-vaccination. Gene modulation was highly uniform across all time points, implying commonality of vaccine responses. Principal components analysis revealed three highly distinct principal groupings: pre-vaccination (-144 h), early (+18 and +48 h), and late post-vaccination (+192 and +336 h). The most significant changes in gene expression occurred at early post-vaccination time points (<=48h), specifically in the induction of pro-inflammatory and innate immunity-related genes. Evidence supporting modulation of innate effector function, specifically antigen processing and presentation by dendritic cells, was especially apparent. Our data indicate that the LVS strain of F. tularensis invokes a strong early response upon vaccination. This pattern of gene regulation may provide insightful information regarding both vaccine efficacy and immunopathogenesis that may provide insight into infection with virulent strains of F. tularensis. Additionally, we obtained valuable information that should prove useful in evaluation of vaccine lots as well as efficacy testing of new anti-F. tularensis vaccines.


systematic_name: M40886
exact_source: Fig 6
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 192h vs 0h in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 192H

description_full:
[cell repeats an earlier one in this file: 1422 characters]


systematic_name: M40887
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/bin/NIHMS29119-supplement-sup_tbl1.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell (2 to 4)d vs 0d in adults (18-32) after exposure to APSV Wetvax , time point 2 to 4D

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M40888
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/#SD1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 28d vs 0d in young adults (21-30) (nonresponder) after exposure to Inactivated influenza vaccine , time point 28D

description_full:
[cell repeats an earlier one in this file: 1385 characters]


systematic_name: M40889
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/bin/NIHMS29119-supplement-sup_tbl1.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell (50 to 60)d vs 0d in adults (18-32) after exposure to APSV Wetvax , time point 50 to 60D

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M40890
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/bin/NIHMS29119-supplement-sup_tbl1.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell (2 to 4)d vs 0d in adults (18-32) after exposure to APSV Wetvax , time point 2 to 4D

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M40891
exact_source: Table 4
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 7d or 14d vs 0d in adults (15-25) after exposure to Attenuvax , time point 7 or 14D , administered subcutaneous

description_full:
  Cellular immunity to measles vaccination is not fully understood at the effector response and gene expression levels. We enrolled 15 healthy individuals (15-25 years old) previously vaccinated with two doses of measles-mumps-rubella-II vaccine to characterize their cellular immunity. We detected a spectrum of lymphoproliferative response (median stimulation indices of 3.4), low precursor frequencies of interferon-gamma (median 0.11%) and interleukin-4 (median 0.05%) by Elispot, and cosecretion of Th1 and Th2 cytokines after measles virus stimulation. Further, global gene expression was examined in five subjects from this cohort after vaccination with an additional dose of measles vaccine (Attenuax, Merck) to identify the genes involved in measles immunity. Linear mixed effect models were used to identify genes significantly up or downregulated in vivo between baseline and Days 7 and 14 after measles vaccination. Measles vaccination induced upregulation of a set of 80 genes, which play a role in measles immunity, signal transduction, apoptosis, cell proliferation, and metabolic pathways. Among the 34 genes that were downregulated, only interferon-alpha is known to have a direct role in measles immunity. This study suggests that measles vaccination leads to activation of multiple cellular mechanisms that can override the immunosuppressant effects of the measles virus and induce immunity.


systematic_name: M40892
exact_source: Supplementary Table 1 (type b)
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146700/bin/mmc1.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in infants (9m) (neonatal) after exposure to Prevnar (USA) , time point 8M

description_full:
  Concerns about the risk of inducing immune deviation-associated neonatal tolerance as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n=104) or at 1, 2 and 3 months of age (infant group, n=105), or to not receive 7vPCV at all (control group, n=109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-gamma) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM(197) and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death.


systematic_name: M40893
exact_source: Fig 2C-F; Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520794/table/T2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with memory B cell response at 28d in peripheral blood mononuclear cell in seniors (50-74) after exposure to Fluarix , time point 28D. Comment: selected pathways: leukocyte migration, MAP kinase activity, cytokine signaling, diabetes of the young

description_full:
  BACKGROUND: Studies suggest that the recall-based humoral immune responses to influenza A/H1N1 originates from activated memory B cells. The aim of this study was to identify baseline, early and late blood transcriptional signatures (in peripheral blood mononuclear cells/PBMCs) associated with memory B cell response following influenza vaccination. METHODS: We used pre- and post-vaccination mRNA-Seq transcriptional profiling on samples from 159 subjects (50-74years old) following receipt of seasonal trivalent influenza vaccine containing the A/California/7/2009/H1N1-like virus, and penalized regression modeling to identify associations with influenza A/H1N1-specific memory B cell ELISPOT response after vaccination. RESULTS: Genesets and genes (p-value range 7.92E(-08) to 0.00018, q-value range 0.00019-0.039) demonstrating significant associations (of gene expression levels) with memory B cell response suggest the importance of metabolic (cholesterol and lipid metabolism-related), cell migration/adhesion, MAP kinase, NF-kB cell signaling (chemokine/cytokine signaling) and transcriptional regulation gene signatures in the development of memory B cell response after influenza vaccination. CONCLUSION: Through an unbiased transcriptome-wide profiling approach, our study identified signatures of memory B cell response following influenza vaccination, highlighting the underappreciated role of metabolic changes (among the other immune function-related events) in the regulation of influenza vaccine-induced immune memory.


systematic_name: M40894
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151076/bin/jiy420_suppl_supplementary_table_1.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in skin of body 6hr vs 0hr in adults (70-93) (VZV challenge) after exposure to Zostavax , time point 6H

description_full:
  Background: The live attenuated vaccine Zostavax was developed to prevent varicella zoster virus (VZV) reactivation that causes herpes zoster (shingles) in older humans. However, the impact of vaccination on the cutaneous response to VZV is not known. Methods: We investigated the response to intradermal VZV antigen challenge before and after Zostavax vaccination in participants > 70 years of age by immunohistological and transcriptomic analyses of skin biopsy specimens collected from the challenge site. Results: Vaccination increased the proportion of VZV-specific CD4+ T cells in the blood and promoted the accumulation of both CD4+ and CD8+ T cells in the skin after VZV antigen challenge. However, Zostavax did not alter the proportion of resident memory T cells (CD4+ and CD8+) or CD4+Foxp3+ regulatory T cells in unchallenged skin. After vaccination, there was increased cutaneous T-cell proliferation at the challenge site and also increased recruitment of T cells from the blood, as indicated by an elevated T-cell migratory gene signature. CD8+ T-cell-associated functional genes were also highly induced in the skin after vaccination. Conclusion: Zostavax vaccination does not alter the abundance of cutaneous resident memory T cells but instead increases the recruitment of VZV-specific T cells from the blood and enhances T-cell activation, particularly cells of the CD8+ subset, in the skin after VZV antigen challenge.


systematic_name: M40895
exact_source: Suppl Table 14
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528489/bin/1208972109_sd01.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with CD8+ T-cell response in peripheral blood mononuclear cell in adults (20-50) after exposure to MRKAd5 HIV-1 gag/pol/nef , time point 3D

description_full:
[cell repeats an earlier one in this file: 1539 characters]


systematic_name: M40896
exact_source: Fig S5 (right)
external_details_URL: http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1519690113/-/DCSupplemental
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 1d postboost vs 0d pre-imm in children (14-27m) after exposure to Imuvac , time point 1D. Comment: TIV

description_full:
  The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4(+) T cells. Compared with transcriptional responses to TIV vaccination previously reported in adults, responses to TIV in infants were markedly attenuated, limited to genes regulating antiviral and antigen presentation pathways, and observed only in a subset of vaccinees. In contrast, transcriptional responses to ATIV boost were more homogenous and robust. Interestingly, a day 1 gene signature characteristic of the innate response (antiviral IFN genes, dendritic cell, and monocyte responses) correlated with hemagglutination at day 28. These findings demonstrate that MF59 enhances the magnitude, kinetics, and consistency of the innate and adaptive response to vaccination with the seasonal influenza vaccine during early childhood, and identify potential molecular correlates of antibody responses.


systematic_name: M40897
exact_source: Fig S5 (left)
external_details_URL: http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1519690113/-/DCSupplemental
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 1d postboost vs 0d pre-imm in children (14-27m) (MF59-adjuvanted) after exposure to Fluad , time point 1D. Comment: ATIV

description_full:
  The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4(+) T cells. Compared with transcriptional responses to TIV vaccination previously reported in adults, responses to TIV in infants were markedly attenuated, limited to genes regulating antiviral and antigen presentation pathways, and observed only in a subset of vaccinees. In contrast, transcriptional responses to ATIV boost were more homogenous and robust. Interestingly, a day 1 gene signature characteristic of the innate response (antiviral IFN genes, dendritic cell, and monocyte responses) correlated with hemagglutination at day 28. These findings demonstrate that MF59 enhances the magnitude, kinetics, and consistency of the innate and adaptive response to vaccination with the seasonal influenza vaccine during early childhood, and identify potential molecular correlates of antibody responses.


systematic_name: M40898
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in T cell 7d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 7D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
  Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses.


systematic_name: M40899
exact_source: Suppl Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072604/bin/ppat.1005892.s003.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with expansion of VZV specific T cells (0d to peak) in peripheral blood mononuclear cell in seniors (50-75) after exposure to Zostavax , time point 1D

description_full:
  Vaccination with attenuated live varicella zoster virus (VZV) can prevent zoster reactivation, but protection is incomplete especially in an older population. To decipher the molecular mechanisms underlying variable vaccine responses, T- and B-cell responses to VZV vaccination were examined in individuals of different ages including identical twin pairs. Contrary to the induction of VZV-specific antibodies, antigen-specific T cell responses were significantly influenced by inherited factors. Diminished generation of long-lived memory T cells in older individuals was mainly caused by increased T cell loss after the peak response while the expansion of antigen-specific T cells was not affected by age. Gene expression in activated CD4 T cells at the time of the peak response identified gene modules related to cell cycle regulation and DNA repair that correlated with the contraction phase of the T cell response and consequently the generation of long-lived memory cells. These data identify cell cycle regulatory mechanisms as targets to reduce T cell attrition in a vaccine response and to improve the generation of antigen-specific T cell memory, in particular in an older population.


systematic_name: M40900
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/table/T2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell post-vaccination vs pre-vaccination in adults (18-40) after exposure to YF-Vax , time point anyD. Comment: Significantly Modulated Genes Common to Vaccinia and Yellow Fever Vaccination

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M40901
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/table/T2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell post-vaccination vs pre-vaccination in adults (18-40) after exposure to APSV Wetvax , time point anyD. Comment: Significantly Modulated Genes Common to Vaccinia and Yellow Fever Vaccination

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M40902
exact_source: Suppl File 1, Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713456/bin/elife-00299-supp1.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with antibody response in blood in adults (18-40) after exposure to Sanofi Pasteur, SA, Inactivated influenza vaccine , time point 0D

description_full:
  Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy. We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine. We identified 20 genes exhibiting a transcriptional response to vaccination, significant genotype effects on gene expression, and correlation between the transcriptional and antibody responses. The results show that variation at the level of genes involved in membrane trafficking and antigen processing significantly influences the human response to influenza vaccination. More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits. DOI:http://dx.doi.org/10.7554/eLife.00299.001.


systematic_name: M40903
exact_source: Abstract
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 3d and 4d vs 0d in children (3-17) after exposure to Fluenz (LAIV) , time point 3D and 4D (merged) , administered i.n.

description_full:
  Live attenuated influenza vaccines (LAIV) can prevent influenza illness and death in children. The absence of known correlates of protection induced by LAIV requires human studies of underlying mechanisms of vaccine-induced immunity, to further elucidate the immunological processes occurring. In this study, children scheduled for elective tonsillectomy were enrolled in a clinical trial to evaluate the immune response to LAIV, in order to compare T and B cell gene expression profiles. Twenty-three children (aged 3-17 years) were divided into 4 groups; unvaccinated controls, or vaccinated intranasally with LAIV at days 3-4, 6-7, and 12-15 before tonsillectomy. Total RNA extraction was performed on tonsillar tissue and high RNA quality was assured. The samples were then analyzed using a validated RT2 Profiler PCR Array containing 84 gene-specific primers involved in B and T cell activation, proliferation, differentiation, regulation and polarization. The gene expression after LAIV vaccination was subsequently compared to the controls. We observed that at d 3-4 post vaccination, 6 genes were down-regulated, namely APC, CD3G, FASLG, IL7, CD8A and TLR1. Meanwhile at 6-7 days post vaccination, 9 genes were significantly up-regulated, including RIPK2, TGFB1, MICB, SOCS1, IL2RA, MS4A1, PTPRC, IL2 and IL8. By days 12-15 the genes RIPK2, IL4, IL12B and TLR2 were overexpressed. RIPK2 was upregulated at all 3 time points. Our data suggests an overall proliferation, differentiation and regulation of B and T cells in the tonsils following LAIV, where the majority of genes were up-regulated at days 6-7 and normalized by days 12-15. These findings may provide a first step into defining future biomarkers or correlates of protection after LAIV immunization.


systematic_name: M40904
exact_source: Suppl Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072604/bin/ppat.1005892.s003.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with contraction of VZV specific T cells (peak to 28d) in peripheral blood mononuclear cell in seniors (50-75) after exposure to Zostavax , time point 1D

description_full:
[cell repeats an earlier one in this file: 1196 characters]


systematic_name: M40905
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/#SD1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 7d vs 0d in young adults (21-30) (nonresponder) after exposure to Inactivated influenza vaccine , time point 7D

description_full:
[cell repeats an earlier one in this file: 1385 characters]


systematic_name: M40906
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946173/bin/mmc1.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell responders vs nonresponders in adults (55-64) after exposure to Fluarix , time point 28D. Comment: Gene expression related to HAI response

description_full:
  To assess gene signatures related to humoral response among healthy older subjects following seasonal influenza vaccination, we studied 94 healthy adults (50-74 years old) who received one documented dose of licensed trivalent influenza vaccine containing the A/California/7/2009 (H1N1)-like virus strain. Influenza-specific antibody (HAI) titer in serum samples and next-generation sequencing on PBMCs were performed using blood samples collected prior to (Day 0) and at two timepoints after (Days 3 and 28) vaccination. We identified a number of uncharacterized genes (ZNF300, NUP1333, KLK1 and others) and confirmed previous studies demonstrating specific genes/genesets that are important mediators of host immune responses and that displayed associations with antibody response to influenza A/H1N1 vaccine. These included interferon-regulatory transcription factors (IRF1/IRF2/IRF6/IRF7/IRF9), chemokine/chemokine receptors (CCR5/CCR9/CCL5), cytokine/cytokine receptors (IFNG/IL10RA/TNFRSF1A), protein kinases (MAP2K4/MAPK3), growth factor receptor (TGFBR1). The identification of gene signatures associated with antibody response represents an early stage in the science for which further research is needed. Such research may assist in the design of better vaccines to facilitate improved defenses against new influenza virus strains, as well as better understanding the genetic drivers of immune responses.


systematic_name: M40907
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946173/bin/mmc1.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell responders vs nonresponders in adults (55-64) after exposure to Fluarix , time point 0D. Comment: Gene expression related to HAI response

description_full:
  To assess gene signatures related to humoral response among healthy older subjects following seasonal influenza vaccination, we studied 94 healthy adults (50-74 years old) who received one documented dose of licensed trivalent influenza vaccine containing the A/California/7/2009 (H1N1)-like virus strain. Influenza-specific antibody (HAI) titer in serum samples and next-generation sequencing on PBMCs were performed using blood samples collected prior to (Day 0) and at two timepoints after (Days 3 and 28) vaccination. We identified a number of uncharacterized genes (ZNF300, NUP1333, KLK1 and others) and confirmed previous studies demonstrating specific genes/genesets that are important mediators of host immune responses and that displayed associations with antibody response to influenza A/H1N1 vaccine. These included interferon-regulatory transcription factors (IRF1/IRF2/IRF6/IRF7/IRF9), chemokine/chemokine receptors (CCR5/CCR9/CCL5), cytokine/cytokine receptors (IFNG/IL10RA/TNFRSF1A), protein kinases (MAP2K4/MAPK3), growth factor receptor (TGFBR1). The identification of gene signatures associated with antibody response represents an early stage in the science for which further research is needed. Such research may assist in the design of better vaccines to facilitate improved defenses against new influenza virus strains, as well as better understanding the genetic drivers of immune responses.


systematic_name: M40908
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/table/T2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell post-vaccination vs pre-vaccination in adults (18-40) after exposure to YF-Vax or APSV Wetvax (identical responses) , time point anyD. Comment: Significantly Modulated Genes Common to Vaccinia and Yellow Fever Vaccination

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M40909
exact_source: Fig 5A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338562/figure/fig05/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with protection in peripheral blood mononuclear cell in unknown after exposure to P. falciparum RTS,S/AS01 , time point 56D

description_full:
  RTS,S is an advanced malaria vaccine candidate and confers significant protection against <i>Plasmodium falciparum</i> infection in humans. Little is known about the molecular mechanisms driving vaccine immunity. Here, we applied a systems biology approach to study immune responses in subjects receiving three consecutive immunizations with RTS,S (RRR), or in those receiving two immunizations of RTS,S/AS01 following a primary immunization with adenovirus 35 (Ad35) (ARR) vector expressing circumsporozoite protein. Subsequent controlled human malaria challenge (CHMI) of the vaccinees with <i>Plasmodium</i>-infected mosquitoes, 3 wk after the final immunization, resulted in ~50% protection in both groups of vaccinees. Circumsporozoite protein (CSP)-specific antibody titers, prechallenge, were associated with protection in the RRR group. In contrast, ARR-induced lower antibody responses, and protection was associated with polyfunctional CD4<sup>+</sup> T-cell responses 2 wk after priming with Ad35. Molecular signatures of B and plasma cells detected in PBMCs were highly correlated with antibody titers prechallenge and protection in the RRR cohort. In contrast, early signatures of innate immunity and dendritic cell activation were highly associated with protection in the ARR cohort. For both vaccine regimens, natural killer (NK) cell signatures negatively correlated with and predicted protection. These results suggest that protective immunity against <i>P. falciparum</i> can be achieved via multiple mechanisms and highlight the utility of systems approaches in defining molecular correlates of protection to vaccination.


systematic_name: M40910
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/bin/aging-07-38-s002.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell seniors vs young adults in seniors (70+), young adults (21-30) after exposure to Inactivated influenza vaccine , time point 0D

description_full:
[cell repeats an earlier one in this file: 1385 characters]


systematic_name: M40911
exact_source: Fig 6C (PO)
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832504/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in CD4-positive, alpha-beta memory T cell 56d vs 0d in adults (18-45) after exposure to BCG vaccine , time point 56D , administered PO (oral). Comment: top 100 most differentially expressed genes comparing Day 0 and Day 56 responses after in vitro re-stimulation with BCG-infected autologous dendritic cells

description_full:
  Protective efficacy of Bacillus Calmette-Guerin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-gamma production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4<sup>+</sup> memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.


systematic_name: M40912
exact_source: Additional File 2, Tab B PPD
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654906/bin/1755-8794-2-10-S2.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in infants (10w) after exposure to BCG (Danish strain BCG Statens Serum Institut, Denmark) , time point 10W. Comment: PBMCs drawn at 10 weeks following immunization at birth

description_full:
  BACKGROUND: Novel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guerin (BCG). Because BCG vaccination is used extensively in infants, this population group is likely to be the first in which efficacy trials of new vaccines will be conducted. However, our understanding of the complexity of immunity to BCG in infants is inadequate, making interpretation of vaccine-induced immune responses difficult. METHODS: To better understand BCG-induced immunity, we performed gene expression profiling in five 10-week old infants routinely vaccinated with BCG at birth. RNA was extracted from 12 hour BCG-stimulated or purified protein derivative of tuberculin (PPD)-stimulated PBMC, isolated from neonatal blood collected 10 weeks after vaccination. RNA was hybridised to the Sentrix(R) HumanRef-8 Expression BeadChip (Illumina) to measure expression of > 16,000 genes. RESULTS: We found that ex vivo stimulation of PBMC with PPD and BCG induced largely similar gene expression profiles, except that BCG induced greater macrophage activation. The peroxisome proliferator-activated receptor (PPAR) signaling pathway, including PPAR-gamma, involved in activation of the alternative, anti-inflammatory macrophage response was down-regulated following stimulation with both antigens. In contrast, up-regulation of genes associated with the classic, pro-inflammatory macrophage response was noted. Further analysis revealed a decrease in the expression of cell adhesion molecules (CAMs), including integrin alpha M (ITGAM), which is known to be important for entry of mycobacteria into the macrophage. Interestingly, more leukocyte genes were down-regulated than up-regulated. CONCLUSION: Our results suggest that a combination of suppressed and up-regulated genes may be key in determining development of protective immunity to TB induced by vaccination with BCG.


systematic_name: M40913
exact_source: Fig 4 & Suppl Table 4
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049462/bin/NIHMS593578-supplement-01.pdf
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes that are components of a model predictive of response in peripheral blood mononuclear cell 7d vs 0d in adults (18-45) after exposure to YF-17D vaccine , time point 7D. Comment: Suppl Table 4: genes validated by ClaNC as being predictive of CD8+ T cell responses from Fig. 4.

description_full:
  A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4-an orchestrator of the integrated stress response-that correlated with and predicted YF-17D CD8(+) T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.


systematic_name: M40914
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/#SD1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 28d vs 0d in young adults (21-30) (nonresponder) after exposure to Inactivated influenza vaccine , time point 28D

description_full:
[cell repeats an earlier one in this file: 1385 characters]


systematic_name: M40915
exact_source: Supplemental Document 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605227/bin/jem.20082292_1.pdf
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 28d vs 0d in unknown after exposure to YF-Vax/Stamaril , time point 28D

description_full:
  Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system.


systematic_name: M40916
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in monocyte 1d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 1D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
  Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses.


systematic_name: M40917
exact_source: Fig 6
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 192h vs 0h in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 192H

description_full:
[cell repeats an earlier one in this file: 1422 characters]


systematic_name: M40918
exact_source: Fig 6
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 336h vs 0h in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 336H

description_full:
[cell repeats an earlier one in this file: 1422 characters]


systematic_name: M40919
exact_source: Fig 6
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 18hr vs 0hr in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 18H

description_full:
[cell repeats an earlier one in this file: 1422 characters]


systematic_name: M40920
exact_source: Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987012/table/pone.0160970.t001/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell vaccinated vs unvaccinated in adolescent/young adults (11-22) (low antibody responders to treatment) after exposure to M-M-R II , time point 7Y

description_full:
  BACKGROUND: There are insufficient system-wide transcriptomic (or other) data that help explain the observed inter-individual variability in antibody titers after measles vaccination in otherwise healthy individuals. METHODS: We performed a transcriptome(mRNA-Seq)-profiling study after in vitro viral stimulation of PBMCs from 30 measles vaccine recipients, selected from a cohort of 764 schoolchildren, based on the highest and lowest antibody titers. We used regression and network biology modeling to define markers associated with neutralizing antibody response. RESULTS: We identified 39 differentially expressed genes that demonstrate significant differences between the high and low antibody responder groups (p-value <= 0.0002, q-value <= 0.092), including the top gene CD93 (p < 1.0E-13, q < 1.0E-09), encoding a receptor required for antigen-driven B-cell differentiation, maintenance of immunoglobulin production and preservation of plasma cells in the bone marrow. Network biology modeling highlighted plasma cell survival (CD93, IL6, CXCL12), chemokine/cytokine activity and cell-cell communication/adhesion/migration as biological processes associated with the observed differential response in the two responder groups. CONCLUSION: We identified genes and pathways that explain in part, and are associated with, neutralizing antibody titers after measles vaccination. This new knowledge could assist in the identification of biomarkers and predictive signatures of protective immunity that may be useful in the design of new vaccine candidates and in clinical studies.


systematic_name: M40921
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/#SD1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 2d vs 0d in seniors (70+) (nonresponder) after exposure to Inactivated influenza vaccine , time point 2D

description_full:
[cell repeats an earlier one in this file: 1385 characters]


systematic_name: M40922
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528489/bin/1208972109_sd01.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (20-50) after exposure to MRKAd5 HIV-1 gag/pol/nef , time point 3D. Comment: Table includes specific cell types

description_full:
[cell repeats an earlier one in this file: 1539 characters]


systematic_name: M40923
exact_source: Fig 5B
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962691/figure/F5/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with high anti-HBs concentration at week 4 post-boost in blood in young/old adults (20-38)/(62-74) (booster vaccination) after exposure to Twinrix , time point 1D. Comment: Correlation between pre-immunization expression levels of single genes (log2-transformed) and anti-HBs concentrations (log10-transformed) at week 4 after booster vaccination

description_full:
  Many current vaccines are less immunogenic and less effective in elderly compared to younger adults due to age-related changes of the immune system. Most vaccines utilized in the elderly contain antigens, which the target population has had previous contact with due to previous vaccination or infection. Therefore, most studies investigating vaccine-induced immune responses in the elderly do not analyze responses to neo-antigens but rather booster responses. However, age-related differences in the immune response could differentially affect primary versus recall responses. We therefore investigated the impact of age on primary and recall antibody responses following hepatitis B vaccination in young and older adults. Focused gene expression profiling was performed before and 1 day after the vaccination in order to identify gene signatures predicting antibody responses. Young (20-40 years; <i>n</i> = 24) and elderly ( > 60 years; <i>n</i> = 17) healthy volunteers received either a primary series (no prior vaccination) or a single booster shot (documented primary vaccination more than 10 years ago). Antibody titers were determined at days 0, 7, and 28, as well as 6 months after the vaccination. After primary vaccination, antibody responses were lower and delayed in the elderly compared to young adults. Non-responders after the three-dose primary series were only observed in the elderly group. Maximum antibody concentrations after booster vaccination were similar in both age groups. Focused gene expression profiling identified 29 transcripts that correlated with age at baseline and clustered in a network centered around type I interferons and pro-inflammatory cytokines. In addition, smaller 8- and 6-gene signatures were identified at baseline that associated with vaccine responsiveness during primary and booster vaccination, respectively. When evaluating the kinetic changes in gene expression profiles before and after primary vaccination, a 33-gene signature, dominated by IFN-signaling, pro-inflammatory cytokines, inflammasome components, and immune cell subset markers, was uncovered that was associated with vaccine responsiveness. By contrast, no such transcripts were identified during booster vaccination. Our results document that primary differs from booster vaccination in old age, in regard to antibody responses as well as at the level of gene signatures. Clinical: www.clinicaltrialsregister.eu, this trial was registered at the EU Clinical Trial Register (EU-CTR) with the EUDRACT-Nr. 2013-002589-38.


systematic_name: M40924
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067885/bin/khvi-14-07-1450122-s001.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell non-responders vs responders in adults (<50) after exposure to Heptatitis B surface antigen vaccine (HBsAg) , time point 3D

description_full:
  Individuals fail to elicit protective antibody after hepatitis B vaccination remain at risk for hepatitis B virus infection. Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) is essential to elucidate the characteristics of gene expression in non-responders. In this study, we enrolled seven responders who had received three injections and seven non-responders who had six injections of hepatitis B vaccine before. All the participants were then vaccinated with a three-dose boost regimen. Microarray analysis and Luminex assay were applied to examine mRNA expression and Th1/Th2/Th9/Th17/Th22/Treg cytokine and chemokine profiles in non-responders and responders. Differentially expressed genes in PBMCs of non-responders at 5 time points, i.e. pre-vaccination, 3<sup>rd</sup>, 7<sup>th</sup>, 28<sup>th</sup> day post the first dose vaccination and 7<sup>th</sup> day post the second dose vaccination indicated a dense network trend. Compared with responders, nine coding genes (BPI, DEFA1B, DEFA4, CEACAM8, MMP8, FOLR3, LTF, TCN1 and TKTL1) were significantly up-regulated in non-responders at all 5 time points, which could probably be the characteristic genes in hepatitis B vaccine non-responsiveness. Gene ontology analysis revealed that most of the DEGs were related with immune responses. Validation results of these 9 genes using quantitative real-time polymerase chain reaction were mostly consistent with the results of microarray. Cytokine analysis demonstrated that IL-27 and CXCL12 concentrations in responders were significantly higher than non-responders on the 3<sup>rd</sup> day after the first dose and 7<sup>th</sup> day after the second dose of vaccination, respectively. No significant difference was observed in other cytokine and chemokine signatures between the two groups. In conclusion, our results revealed characteristic transcriptome and cytokine changes in hepatitis B vaccine non-responders after boost immunization.


systematic_name: M40925
exact_source: Fig 3C
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067885/figure/f0003/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell non-responders vs responders in adults (<50) after exposure to Heptatitis B surface antigen vaccine (HBsAg) , time point 0, 3, 7, 28 and 35 jointly. Comment: these genes were upregulated at all five timepoints

description_full:
  Individuals fail to elicit protective antibody after hepatitis B vaccination remain at risk for hepatitis B virus infection. Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) is essential to elucidate the characteristics of gene expression in non-responders. In this study, we enrolled seven responders who had received three injections and seven non-responders who had six injections of hepatitis B vaccine before. All the participants were then vaccinated with a three-dose boost regimen. Microarray analysis and Luminex assay were applied to examine mRNA expression and Th1/Th2/Th9/Th17/Th22/Treg cytokine and chemokine profiles in non-responders and responders. Differentially expressed genes in PBMCs of non-responders at 5 time points, i.e. pre-vaccination, 3<sup>rd</sup>, 7<sup>th</sup>, 28<sup>th</sup> day post the first dose vaccination and 7<sup>th</sup> day post the second dose vaccination indicated a dense network trend. Compared with responders, nine coding genes (BPI, DEFA1B, DEFA4, CEACAM8, MMP8, FOLR3, LTF, TCN1 and TKTL1) were significantly up-regulated in non-responders at all 5 time points, which could probably be the characteristic genes in hepatitis B vaccine non-responsiveness. Gene ontology analysis revealed that most of the DEGs were related with immune responses. Validation results of these 9 genes using quantitative real-time polymerase chain reaction were mostly consistent with the results of microarray. Cytokine analysis demonstrated that IL-27 and CXCL12 concentrations in responders were significantly higher than non-responders on the 3<sup>rd</sup> day after the first dose and 7<sup>th</sup> day after the second dose of vaccination, respectively. No significant difference was observed in other cytokine and chemokine signatures between the two groups. In conclusion, our results revealed characteristic transcriptome and cytokine changes in hepatitis B vaccine non-responders after boost immunization.


systematic_name: M40927
exact_source: Fig 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700883/figure/pone-0067922-g001/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 2d vs 0d in adult (18-55) after exposure to Modified Vaccinia Ankara (MVA) virus vaccine vector , time point 2D

description_full:
  A better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-gamma (IFN-gamma) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Ralpha two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.


systematic_name: M40928
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/#SD1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 2d vs 0d in seniors (70+) (nonresponder) after exposure to Inactivated influenza vaccine , time point 2D

description_full:
[cell repeats an earlier one in this file: 1385 characters]


systematic_name: M40929
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946173/bin/mmc1.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell responders vs nonresponders in adults (55-64) after exposure to Fluarix , time point 28D. Comment: Gene expression related to HAI response

description_full:
  To assess gene signatures related to humoral response among healthy older subjects following seasonal influenza vaccination, we studied 94 healthy adults (50-74 years old) who received one documented dose of licensed trivalent influenza vaccine containing the A/California/7/2009 (H1N1)-like virus strain. Influenza-specific antibody (HAI) titer in serum samples and next-generation sequencing on PBMCs were performed using blood samples collected prior to (Day 0) and at two timepoints after (Days 3 and 28) vaccination. We identified a number of uncharacterized genes (ZNF300, NUP1333, KLK1 and others) and confirmed previous studies demonstrating specific genes/genesets that are important mediators of host immune responses and that displayed associations with antibody response to influenza A/H1N1 vaccine. These included interferon-regulatory transcription factors (IRF1/IRF2/IRF6/IRF7/IRF9), chemokine/chemokine receptors (CCR5/CCR9/CCL5), cytokine/cytokine receptors (IFNG/IL10RA/TNFRSF1A), protein kinases (MAP2K4/MAPK3), growth factor receptor (TGFBR1). The identification of gene signatures associated with antibody response represents an early stage in the science for which further research is needed. Such research may assist in the design of better vaccines to facilitate improved defenses against new influenza virus strains, as well as better understanding the genetic drivers of immune responses.


systematic_name: M40930
exact_source: Supplementary Table 2a: LAIV-Monocytes
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-3.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in monocyte 7d vs 0d in young adults (18-50) after exposure to FluMist , time point 7D

description_full:
  Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons. We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). TIV induced higher antibody titers and more plasmablasts than LAIV did. In subjects vaccinated with TIV, early molecular signatures correlated with and could be used to accurately predict later antibody titers in two independent trials. Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-specific antibody titers, which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses. Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.


systematic_name: M40931
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in monocyte 1d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 1D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M40932
exact_source: Fig 5b
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/figure/F5/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-45) (anti-DT antibody-correlation profile) after exposure to Menactra , time point 3D

description_full:
  Many vaccines induce protective immunity via antibodies. Systems biology approaches have been used to determine signatures that can be used to predict vaccine-induced immunity in humans, but whether there is a 'universal signature' that can be used to predict antibody responses to any vaccine is unknown. Here we did systems analyses of immune responses to the polysaccharide and conjugate vaccines against meningococcus in healthy adults, in the broader context of published studies of vaccines against yellow fever virus and influenza virus. To achieve this, we did a large-scale network integration of publicly available human blood transcriptomes and systems-scale databases in specific biological contexts and deduced a set of transcription modules in blood. Those modules revealed distinct transcriptional signatures of antibody responses to different classes of vaccines, which provided key insights into primary viral, protein recall and anti-polysaccharide responses. Our results elucidate the early transcriptional programs that orchestrate vaccine immunity in humans and demonstrate the power of integrative network modeling.


systematic_name: M40933
exact_source: Fig 5b
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/figure/F5/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-45) after exposure to Menomune A/C/Y/W-135 , time point 3D

description_full:
  Many vaccines induce protective immunity via antibodies. Systems biology approaches have been used to determine signatures that can be used to predict vaccine-induced immunity in humans, but whether there is a 'universal signature' that can be used to predict antibody responses to any vaccine is unknown. Here we did systems analyses of immune responses to the polysaccharide and conjugate vaccines against meningococcus in healthy adults, in the broader context of published studies of vaccines against yellow fever virus and influenza virus. To achieve this, we did a large-scale network integration of publicly available human blood transcriptomes and systems-scale databases in specific biological contexts and deduced a set of transcription modules in blood. Those modules revealed distinct transcriptional signatures of antibody responses to different classes of vaccines, which provided key insights into primary viral, protein recall and anti-polysaccharide responses. Our results elucidate the early transcriptional programs that orchestrate vaccine immunity in humans and demonstrate the power of integrative network modeling.


systematic_name: M40934
exact_source: Fig 5b
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/figure/F5/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-45) (anti-polysaccharide antibody-correlation profile) after exposure to Menactra , time point 3D

description_full:
  Many vaccines induce protective immunity via antibodies. Systems biology approaches have been used to determine signatures that can be used to predict vaccine-induced immunity in humans, but whether there is a 'universal signature' that can be used to predict antibody responses to any vaccine is unknown. Here we did systems analyses of immune responses to the polysaccharide and conjugate vaccines against meningococcus in healthy adults, in the broader context of published studies of vaccines against yellow fever virus and influenza virus. To achieve this, we did a large-scale network integration of publicly available human blood transcriptomes and systems-scale databases in specific biological contexts and deduced a set of transcription modules in blood. Those modules revealed distinct transcriptional signatures of antibody responses to different classes of vaccines, which provided key insights into primary viral, protein recall and anti-polysaccharide responses. Our results elucidate the early transcriptional programs that orchestrate vaccine immunity in humans and demonstrate the power of integrative network modeling.


systematic_name: M40935
exact_source: Supplementary Fig 13
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/bin/NIHMS540680-supplement-13.jpg
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-45) (anti-DT antibody-correlation profile) after exposure to Menactra , time point 3D

description_full:
[cell repeats an earlier one in this file: 1137 characters]


systematic_name: M40936
exact_source: Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551876/table/T3/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 24h vs 0h in adults (18-45) (non-responders (previously immunized)) after exposure to Live attenuated vaccine TC-83 , time point 24H. Comment: initial exposure 2-10 months before PBMCs drawn. significant genes chosen for membership in canonical pathways

description_full:
  Venezuelan equine encephalitis virus (VEEV) is a positive-strand RNA Alphavirus endemic in Central and South America, and the causative agent of fatal encephalitis in humans. In an effort to better understand the mechanisms of infection, including differences between people who produce a neutralizing antibody response to the vaccine and those who do not, we performed whole genome transcriptional analysis in human PBMCs exposed in vitro to the live-attenuated vaccine strain of VEEV, TC-83. We compared the molecular responses in cells from three groups of individuals: naive; previously vaccinated individuals who developed a neutralizing antibody response to the vaccine (responders); and those who did not develop a neutralizing antibody response to the vaccine (nonresponders). Overall, the changes in gene expression were more intense for the naive group after TC-83 challenge and least potent in the nonresponder group. The main canonical pathways revealed the involvement of interferon and interferon-induced pathways, as well as toll-like receptors TLR- and interleukin (IL)-12-related pathways. HLA class II genotype and suppression of transcript expression for TLR2, TLR4 and TLR8 in the nonresponder group may help explain the lack of vaccine response in this study group. Because TL3 and TLR7 transcripts were elevated in all study groups, these factors may be indicators of the infection and not the immunological state of the individuals. Biomarkers were identified that differentiate between the vaccine responder and the vaccine nonresponder groups. The identified biomarkers were contrasted against transcripts that were unique to the naive population alone upon induction with TC-83. Biomarker analysis allowed for the discernment between the naive (innate) responses; the responder (recall) responses; and the nonresponder (alternative) changes to gene transcription that were caused by infection with TC-83. The study also points to the existence of HLA haplotypes that may discriminate between vaccine low- and high-responder phenotypes.


systematic_name: M40937
exact_source: S1 Table
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443534/bin/pntd.0005527.s002.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 24hr vs 0hr in adults (18-50) (high dose subjects) after exposure to ChAd63-KH , time point 24H , administered Intramuscular injection. Comment: DE gene list for high dose subjects.

description_full:
  BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFN-gamma ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359).


systematic_name: M40938
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500554/bin/jiy721_suppl_supplementary_table_1a.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell vaccinated with AS03 adjuvant vs phosphate-bufferred saline in adults (19-39) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 1D , administered i.m.

description_full:
  BACKGROUND: Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood. METHODS: Using ribonucleic acid sequencing on peripheral blood mononuclear cells (PBMCs) from AS03-adjuvanted and unadjuvanted inactivated H5N1 vaccine recipients, we identified differentially expressed genes, enriched pathways, and genes that correlated with serologic responses. We compared bulk PBMC findings with our previously published assessments of flow-sorted immune cell types. RESULTS: AS03-adjuvanted vaccine induced the strongest differential signals on day 1 postvaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, Fcgamma receptor (FcgammaR)-mediated phagocytosis, and antigen processing and presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared with individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMCs, and several pathways identified in individual cell types were absent in PBMCs. CONCLUSIONS: Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5- to 8-fold upregulation of Fc-gammaR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. Although PBMCs and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.


systematic_name: M40939
exact_source: Supplementary Table 2a: LAIV-Bcells
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-3.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in B cell 7d vs 0d in young adults (18-50) after exposure to FluMist , time point 7D

description_full:
  Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons. We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). TIV induced higher antibody titers and more plasmablasts than LAIV did. In subjects vaccinated with TIV, early molecular signatures correlated with and could be used to accurately predict later antibody titers in two independent trials. Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-specific antibody titers, which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses. Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.


systematic_name: M40940
exact_source: Suppl File 1, Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713456/bin/elife-00299-supp1.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with antibody response in blood in adults (18-40) after exposure to Sanofi Pasteur, SA, Inactivated influenza vaccine , time point 14D

description_full:
  Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy. We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine. We identified 20 genes exhibiting a transcriptional response to vaccination, significant genotype effects on gene expression, and correlation between the transcriptional and antibody responses. The results show that variation at the level of genes involved in membrane trafficking and antigen processing significantly influences the human response to influenza vaccination. More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits. DOI:http://dx.doi.org/10.7554/eLife.00299.001.


systematic_name: M40941
exact_source: Table S1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700883/bin/pone.0067922.s004.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell vaccinated vs control in adults (18-55) (treated in vitro with MVA85A) after exposure to Modified Vaccinia Ankara (MVA) virus vaccine vector , time point 6H

description_full:
  A better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-gamma (IFN-gamma) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Ralpha two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.


systematic_name: M40942
exact_source: Table 2, NFKB1 and NFKB2 mentioned in text
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583508/table/tbl2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 1d vs 0d in adults (18-55) after exposure to rVSV-ZEBOV , time point 1D

description_full:
  Predicting vaccine efficacy remains a challenge. We used a systems vaccinology approach to identify early innate immune correlates of antibody induction in humans receiving the Ebola vaccine rVSV-ZEBOV. Blood samples from days 0, 1, 3, 7, and 14 were analyzed for changes in cytokine levels, innate immune cell subsets, and gene expression. Integrative statistical analyses with cross-validation identified a signature of 5 early innate markers correlating with antibody titers on day 28 and beyond. Among those, IP-10 on day 3 and MFI of CXCR6 on NK cells on day 1 were independent correlates. Consistently, we found an early gene expression signature linked to IP-10. This comprehensive characterization of early innate immune responses to the rVSV-ZEBOV vaccine in humans revealed immune signatures linked to IP-10. These results suggest correlates of vaccine-induced antibody induction and provide a rationale to explore strategies for augmenting the effectiveness of vaccines through manipulation of IP-10.


systematic_name: M40943
exact_source: Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987012/table/pone.0160970.t001/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell vaccinated vs unvaccinated in adolescent/young adults (11-22) (high antibody responders to treatment) after exposure to M-M-R II , time point 7Y

description_full:
  BACKGROUND: There are insufficient system-wide transcriptomic (or other) data that help explain the observed inter-individual variability in antibody titers after measles vaccination in otherwise healthy individuals. METHODS: We performed a transcriptome(mRNA-Seq)-profiling study after in vitro viral stimulation of PBMCs from 30 measles vaccine recipients, selected from a cohort of 764 schoolchildren, based on the highest and lowest antibody titers. We used regression and network biology modeling to define markers associated with neutralizing antibody response. RESULTS: We identified 39 differentially expressed genes that demonstrate significant differences between the high and low antibody responder groups (p-value <= 0.0002, q-value <= 0.092), including the top gene CD93 (p < 1.0E-13, q < 1.0E-09), encoding a receptor required for antigen-driven B-cell differentiation, maintenance of immunoglobulin production and preservation of plasma cells in the bone marrow. Network biology modeling highlighted plasma cell survival (CD93, IL6, CXCL12), chemokine/cytokine activity and cell-cell communication/adhesion/migration as biological processes associated with the observed differential response in the two responder groups. CONCLUSION: We identified genes and pathways that explain in part, and are associated with, neutralizing antibody titers after measles vaccination. This new knowledge could assist in the identification of biomarkers and predictive signatures of protective immunity that may be useful in the design of new vaccine candidates and in clinical studies.


systematic_name: M40944
exact_source: Suppl Table III
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701477/bin/NIHMS83712-supplement-Supplemetary_t.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with antibody response in peripheral blood mononuclear cell in young adults (18-25) after exposure to HPV-16 L1 VLP , time point 7M. Comment: Spearman Correlation of Gene Expression with Neutralizing Antibody Levels

description_full:
  Human papillomavirus (HPV) virus-like particle (VLP) vaccines were recently licensed. Although neutralizing Ab titers are thought to be the main effectors of protection against infection, early predictors of long-term efficacy are not yet defined and a comprehensive understanding of innate and adaptive immune responses to vaccination is still lacking. Here, microarrays were used to compare the gene expression signature in HPV-16 L1 VLP-stimulated PBMCs from 17 vaccine and 4 placebo recipients before vaccination and 1 mo after receiving the second immunization. Vaccination with a monovalent HPV-16 L1 VLP vaccine was associated with modulation of genes involved in the inflammatory/defense response, cytokine, IFN, and cell cycle pathways in VLP-stimulated PBMCs. Additionally, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing Ab titers were found for cyclin D2 (CCND2) and galectin (LGALS2). Twenty-two differentially expressed probesets were selected for confirmation by RT-PCR in an independent sample set. Agreement with microarray data was seen for more than two-thirds of these probesets. Up-regulation of immune/defense response genes by HPV-16 L1 VLP, in particular, IFN-induced genes, was observed in PBMCs collected before vaccination, with many of these genes being further induced following vaccination. In conclusion, we identified important innate and adaptive response-related genes induced by vaccination with HPV-16 L1 VLP. Further studies are needed to identify gene expression signatures of immunogenicity and long-term protection with potential utility in prediction of long-term HPV vaccination outcomes in clinical trials.


systematic_name: M40945
exact_source: Suppl Table III
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701477/bin/NIHMS83712-supplement-Supplemetary_t.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with antibody response in peripheral blood mononuclear cell in young adults (18-25) after exposure to HPV-16 L1 VLP , time point 12M. Comment: Spearman Correlation of Gene Expression with Neutralizing Antibody Levels

description_full:
  Human papillomavirus (HPV) virus-like particle (VLP) vaccines were recently licensed. Although neutralizing Ab titers are thought to be the main effectors of protection against infection, early predictors of long-term efficacy are not yet defined and a comprehensive understanding of innate and adaptive immune responses to vaccination is still lacking. Here, microarrays were used to compare the gene expression signature in HPV-16 L1 VLP-stimulated PBMCs from 17 vaccine and 4 placebo recipients before vaccination and 1 mo after receiving the second immunization. Vaccination with a monovalent HPV-16 L1 VLP vaccine was associated with modulation of genes involved in the inflammatory/defense response, cytokine, IFN, and cell cycle pathways in VLP-stimulated PBMCs. Additionally, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing Ab titers were found for cyclin D2 (CCND2) and galectin (LGALS2). Twenty-two differentially expressed probesets were selected for confirmation by RT-PCR in an independent sample set. Agreement with microarray data was seen for more than two-thirds of these probesets. Up-regulation of immune/defense response genes by HPV-16 L1 VLP, in particular, IFN-induced genes, was observed in PBMCs collected before vaccination, with many of these genes being further induced following vaccination. In conclusion, we identified important innate and adaptive response-related genes induced by vaccination with HPV-16 L1 VLP. Further studies are needed to identify gene expression signatures of immunogenicity and long-term protection with potential utility in prediction of long-term HPV vaccination outcomes in clinical trials.


systematic_name: M40946
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in monocyte 7d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 7D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M40947
exact_source: s4_dnc_d3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in dendritic cell 3d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 3D , administered i.m.

description_full:
  BACKGROUND: Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. OBJECTIVE: We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18-49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. RESULTS: Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. CONCLUSIONS: Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. TRIAL: ClinicalTrials.gov NCT01573312.


systematic_name: M40948
exact_source: Fig 6
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 48h vs 0h in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 48H

description_full:
[cell repeats an earlier one in this file: 1422 characters]


systematic_name: M40949
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in infants (9m) after exposure to Prevnar (USA) , time point 9M and 8M (identical response signature)

description_full:
  Concerns about the risk of inducing immune deviation-associated neonatal tolerance as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n=104) or at 1, 2 and 3 months of age (infant group, n=105), or to not receive 7vPCV at all (control group, n=109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-gamma) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM(197) and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death.


systematic_name: M40950
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in B cell 7d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 7D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M40951
exact_source: Suppl mat, 2016HV0244R-s01.xlsx
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287313/bin/khvi-13-01-1227900-s001.zip
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood vaccinated vs control in adults (23-48) after exposure to Live attenuated vaccine TC-83 , time point 2D

description_full:
  Venezuelan equine encephalitis virus (VEEV) is an important human and animal alphavirus pathogen transmitted by mosquitoes. The virus is endemic in Central and South America, but has also caused equine outbreaks in southwestern areas of the United States. In an effort to better understand the molecular mechanisms of the development of immunity to this important pathogen, we performed transcriptional analysis from whole, unfractionated human blood of patients who had been immunized with the live-attenuated vaccine strain of VEEV, TC-83. We compared changes in the transcriptome between naive individuals who were mock vaccinated with saline to responses of individuals who received TC-83. Significant transcriptional changes were noted at days 2, 7, and 14 following vaccination. The top canonical pathways revealed at early and intermediate time points (days 2 and 7) included the involvement of the classic interferon response, interferon-response factors, activation of pattern recognition receptors, and engagement of the inflammasome. By day 14, the top canonical pathways included oxidative phosphorylation, the protein ubiquitination pathway, natural killer cell signaling, and B-cell development. Biomarkers were identified that differentiate between vaccinees and control subjects, at early, intermediate, and late stages of the development of immunity as well as markers which were common to all 3 stages following vaccination but distinct from the sham-vaccinated control subjects. The study represents a novel examination of molecular processes that lead to the development of immunity against VEEV in humans and which may be of value as diagnostic targets, to enhance modern vaccine design, or molecular correlates of protection.


systematic_name: M40952
exact_source: Supplementary Table 1 (type c)
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146700/bin/mmc1.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in infants (9m) (infant) after exposure to Prevnar (USA) , time point 9M

description_full:
  Concerns about the risk of inducing immune deviation-associated neonatal tolerance as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n=104) or at 1, 2 and 3 months of age (infant group, n=105), or to not receive 7vPCV at all (control group, n=109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-gamma) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM(197) and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death.


systematic_name: M40953
exact_source: Fig 3A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700883/figure/pone-0067922-g003/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell high responders vs low responders in adult (18-55) after exposure to Modified Vaccinia Ankara (MVA) virus vaccine vector , time point 0D. Comment: genes part of classifier

description_full:
  A better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-gamma (IFN-gamma) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Ralpha two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.


systematic_name: M40954
exact_source: Supplemental Document 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605227/bin/jem.20082292_1.pdf
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 14d vs 0d in unknown after exposure to YF-Vax/Stamaril , time point 14D

description_full:
  Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system.


systematic_name: M40955
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in neutrophil 7d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 7D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M40956
exact_source: Fig 4C-D
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763735/figure/fig04/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 1d postboost vs 0d pre-imm in children (14-27m) (MF59-adjuvanted) after exposure to Fluad , time point 1D. Comment: (C) Genes in BTM M40; (D) Genes in BTM M53

description_full:
  The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4(+) T cells. Compared with transcriptional responses to TIV vaccination previously reported in adults, responses to TIV in infants were markedly attenuated, limited to genes regulating antiviral and antigen presentation pathways, and observed only in a subset of vaccinees. In contrast, transcriptional responses to ATIV boost were more homogenous and robust. Interestingly, a day 1 gene signature characteristic of the innate response (antiviral IFN genes, dendritic cell, and monocyte responses) correlated with hemagglutination at day 28. These findings demonstrate that MF59 enhances the magnitude, kinetics, and consistency of the innate and adaptive response to vaccination with the seasonal influenza vaccine during early childhood, and identify potential molecular correlates of antibody responses.


systematic_name: M40957
exact_source: Fig 5A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962691/figure/F5/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with high anti-HBs concentration at week 30 in blood in young/old adults (20-40)/(60-84) (primary vaccination) after exposure to Twinrix , time point 1D. Comment: Correlation between pre-immunization expression levels of single genes (log2-transformed) and anti-HBs concentrations (log10-transformed) at week 30 post-primary vaccination

description_full:
  Many current vaccines are less immunogenic and less effective in elderly compared to younger adults due to age-related changes of the immune system. Most vaccines utilized in the elderly contain antigens, which the target population has had previous contact with due to previous vaccination or infection. Therefore, most studies investigating vaccine-induced immune responses in the elderly do not analyze responses to neo-antigens but rather booster responses. However, age-related differences in the immune response could differentially affect primary versus recall responses. We therefore investigated the impact of age on primary and recall antibody responses following hepatitis B vaccination in young and older adults. Focused gene expression profiling was performed before and 1 day after the vaccination in order to identify gene signatures predicting antibody responses. Young (20-40 years; <i>n</i> = 24) and elderly ( > 60 years; <i>n</i> = 17) healthy volunteers received either a primary series (no prior vaccination) or a single booster shot (documented primary vaccination more than 10 years ago). Antibody titers were determined at days 0, 7, and 28, as well as 6 months after the vaccination. After primary vaccination, antibody responses were lower and delayed in the elderly compared to young adults. Non-responders after the three-dose primary series were only observed in the elderly group. Maximum antibody concentrations after booster vaccination were similar in both age groups. Focused gene expression profiling identified 29 transcripts that correlated with age at baseline and clustered in a network centered around type I interferons and pro-inflammatory cytokines. In addition, smaller 8- and 6-gene signatures were identified at baseline that associated with vaccine responsiveness during primary and booster vaccination, respectively. When evaluating the kinetic changes in gene expression profiles before and after primary vaccination, a 33-gene signature, dominated by IFN-signaling, pro-inflammatory cytokines, inflammasome components, and immune cell subset markers, was uncovered that was associated with vaccine responsiveness. By contrast, no such transcripts were identified during booster vaccination. Our results document that primary differs from booster vaccination in old age, in regard to antibody responses as well as at the level of gene signatures. Clinical: www.clinicaltrialsregister.eu, this trial was registered at the EU Clinical Trial Register (EU-CTR) with the EUDRACT-Nr. 2013-002589-38.


systematic_name: M40958
exact_source: Table III, see also Suppl Table III
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 2m vs 0m in young adults (18-25) after exposure to HPV-16 L1 VLP , time point 2M. Comment: Gene Expression with Neutralizing Antibody Levels

description_full:
  Human papillomavirus (HPV) virus-like particle (VLP) vaccines were recently licensed. Although neutralizing Ab titers are thought to be the main effectors of protection against infection, early predictors of long-term efficacy are not yet defined and a comprehensive understanding of innate and adaptive immune responses to vaccination is still lacking. Here, microarrays were used to compare the gene expression signature in HPV-16 L1 VLP-stimulated PBMCs from 17 vaccine and 4 placebo recipients before vaccination and 1 mo after receiving the second immunization. Vaccination with a monovalent HPV-16 L1 VLP vaccine was associated with modulation of genes involved in the inflammatory/defense response, cytokine, IFN, and cell cycle pathways in VLP-stimulated PBMCs. Additionally, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing Ab titers were found for cyclin D2 (CCND2) and galectin (LGALS2). Twenty-two differentially expressed probesets were selected for confirmation by RT-PCR in an independent sample set. Agreement with microarray data was seen for more than two-thirds of these probesets. Up-regulation of immune/defense response genes by HPV-16 L1 VLP, in particular, IFN-induced genes, was observed in PBMCs collected before vaccination, with many of these genes being further induced following vaccination. In conclusion, we identified important innate and adaptive response-related genes induced by vaccination with HPV-16 L1 VLP. Further studies are needed to identify gene expression signatures of immunogenicity and long-term protection with potential utility in prediction of long-term HPV vaccination outcomes in clinical trials.

external_details_URL:
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701477/table/T3/| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701477/bin/NIHMS83712-supplement-Supplemetary_t.doc


systematic_name: M40959
exact_source: Supplementary Fig 13
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/bin/NIHMS540680-supplement-13.jpg
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with antibody response in peripheral blood mononuclear cell in adults (18-45) (anti-DT antibody-correlation profile) after exposure to Menactra , time point 3D

description_full:
[cell repeats an earlier one in this file: 1137 characters]


systematic_name: M40960
exact_source: Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/table/T3/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell (18 to 48)h vs 0h in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 18 to 48H. Comment: Pattern 4, down early. These 21 of 56 genes in pattern linked to immune-related functions.

description_full:
[cell repeats an earlier one in this file: 1422 characters]


systematic_name: M40961
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in B cell 3d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 3D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M40962
exact_source: Suppl Table, see also Fig 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712333/bin/aging-07-1077-s001.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood cohort 1 (re-vaccinated in 6-9 months) vs cohort 2 (re-vaccinated in 12-13 months) in adults (65+) after exposure to 2012-2013 seasonal trivalent inactivated influenza vaccine (TIV) , time point N/A. Comment: Cohort 1 (re-vaccinated in 6-9 months) vs Cohort 2 (re-vaccinated in 12-13 months)

description_full:
  We tested antibody responses to the trivalent inactivated influenza vaccine (TIV) in 34 aged individuals ( > 65 yrs) during the 2012/13 vaccination seasons. Nearly all had been vaccinated the previous year although the time interval between the two vaccine doses differed. One subgroup was re-vaccinated in 2012/13 within 6-9 months of their 2011/12 vaccination, the other received the two doses of vaccine in the typical ~12 month interval. Unexpectedly the sub-cohort with early revaccination exhibited significantly increased response rates and antibody titers to TIV compared to their normally re-vaccinated aged counter parts. Microarray analyses of gene expression in whole blood RNA taken at the day of the 2012/13 re-vaccination revealed statistically significant differences in expression of 754 genes between the individuals with early re-vaccination compared to subjects vaccinated in a normal 12 month interval. These observations suggest that TIV has long-lasting effects on the immune system affecting B cell responses as well as the transcriptome of peripheral blood mononuclear cells and this residual effect may augment vaccination response in patients where the effect of the previous vaccination has not yet diminished.


systematic_name: M40963
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in B cell 7d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 7D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M40964
exact_source: Fig 5b
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/figure/F5/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-45) (anti-polysaccharide antibody-correlation profile) after exposure to Menactra , time point 3D

description_full:
[cell repeats an earlier one in this file: 1137 characters]


systematic_name: M40965
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834766/bin/Table_2.XLSX
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 3d vs 0hr in adults (18-45) after exposure to CN54gp140 adjuvanted with GLA-AF , time point 3D , administered i.m.

description_full:
  Systems biology approaches have recently provided new insights into the mechanisms of action of human vaccines and adjuvants. Here, we investigated early transcriptional signatures induced in whole blood of healthy subjects following vaccination with a recombinant HIV-1 envelope glycoprotein subunit CN54gp140 adjuvanted with the TLR4 agonist glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) and correlated signatures to CN54gp140-specific serum antibody responses. Fourteen healthy volunteers aged 18-45 years were immunized intramuscularly three times at 1-month intervals and whole blood samples were collected at baseline, 6 h, and 1, 3, and 7 days post first immunization. Subtle changes in the transcriptomic profiles were observed following immunization, ranging from over 300 differentially expressed genes (DEGs) at day 1 to nearly 100 DEGs at day 7 following immunization. Functional pathway analysis revealed blood transcription modules (BTMs) related to general cell cycle activation, and innate immune cell activation at early time points, as well as BTMs related to T cells and B cell activation at the later time points post-immunization. Diverse CN54gp140-specific serum antibody responses of the subjects enabled their categorization into high or low responders, at early ( < 1 month) and late (up to 6 months) time points post vaccination. BTM analyses revealed repression of modules enriched in NK cells, and the mitochondrial electron chain, in individuals with high or sustained antigen-specific antibody responses. However, low responders showed an enhancement of BTMs associated with enrichment in myeloid cells and monocytes as well as integrin cell surface interactions. Flow cytometry analysis of peripheral blood mononuclear cells obtained from the subjects revealed an enhanced frequency of CD56<sup>dim</sup> NK cells in the majority of vaccines 14 days after vaccination as compared with the baseline. These results emphasize the utility of a systems biology approach to enhance our understanding on the mechanisms of action of TLR4 adjuvanted human vaccines.


systematic_name: M40966
exact_source: Table 1: Late gene expression (Day 28 - Day 0)
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520794/table/T1/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with memory B cell response in peripheral blood mononuclear cell in adults (50-74) after exposure to trivalent inactivated vaccine (A/California/7/09 (H1N1,), A/Perth /16/2009 (H3N2), and B/Brisbane/60/2008). , time point 28D. Comment: Association of baseline, early and late gene expression changes with peak memory B cell ELISPOT response (Day 28 - Day 0) in older individuals

description_full:
  BACKGROUND: Studies suggest that the recall-based humoral immune responses to influenza A/H1N1 originates from activated memory B cells. The aim of this study was to identify baseline, early and late blood transcriptional signatures (in peripheral blood mononuclear cells/PBMCs) associated with memory B cell response following influenza vaccination. METHODS: We used pre- and post-vaccination mRNA-Seq transcriptional profiling on samples from 159 subjects (50-74years old) following receipt of seasonal trivalent influenza vaccine containing the A/California/7/2009/H1N1-like virus, and penalized regression modeling to identify associations with influenza A/H1N1-specific memory B cell ELISPOT response after vaccination. RESULTS: Genesets and genes (p-value range 7.92E(-08) to 0.00018, q-value range 0.00019-0.039) demonstrating significant associations (of gene expression levels) with memory B cell response suggest the importance of metabolic (cholesterol and lipid metabolism-related), cell migration/adhesion, MAP kinase, NF-kB cell signaling (chemokine/cytokine signaling) and transcriptional regulation gene signatures in the development of memory B cell response after influenza vaccination. CONCLUSION: Through an unbiased transcriptome-wide profiling approach, our study identified signatures of memory B cell response following influenza vaccination, highlighting the underappreciated role of metabolic changes (among the other immune function-related events) in the regulation of influenza vaccine-induced immune memory.


systematic_name: M40967
exact_source: s4_nkc_d1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in natural killer cell 1d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 1D , administered i.m.

description_full:
  BACKGROUND: Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. OBJECTIVE: We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18-49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. RESULTS: Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. CONCLUSIONS: Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. TRIAL: ClinicalTrials.gov NCT01573312.


systematic_name: M40968
exact_source: Table 5
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/table/T5/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell (18 to 48)h vs 0h in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 18 to 48H. Comment: Pattern 6, up early

description_full:
[cell repeats an earlier one in this file: 1422 characters]


systematic_name: M40969
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067885/bin/khvi-14-07-1450122-s001.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell non-responders vs responders in adults (<50) after exposure to Heptatitis B surface antigen vaccine (HBsAg) , time point 0D

description_full:
  Individuals fail to elicit protective antibody after hepatitis B vaccination remain at risk for hepatitis B virus infection. Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) is essential to elucidate the characteristics of gene expression in non-responders. In this study, we enrolled seven responders who had received three injections and seven non-responders who had six injections of hepatitis B vaccine before. All the participants were then vaccinated with a three-dose boost regimen. Microarray analysis and Luminex assay were applied to examine mRNA expression and Th1/Th2/Th9/Th17/Th22/Treg cytokine and chemokine profiles in non-responders and responders. Differentially expressed genes in PBMCs of non-responders at 5 time points, i.e. pre-vaccination, 3<sup>rd</sup>, 7<sup>th</sup>, 28<sup>th</sup> day post the first dose vaccination and 7<sup>th</sup> day post the second dose vaccination indicated a dense network trend. Compared with responders, nine coding genes (BPI, DEFA1B, DEFA4, CEACAM8, MMP8, FOLR3, LTF, TCN1 and TKTL1) were significantly up-regulated in non-responders at all 5 time points, which could probably be the characteristic genes in hepatitis B vaccine non-responsiveness. Gene ontology analysis revealed that most of the DEGs were related with immune responses. Validation results of these 9 genes using quantitative real-time polymerase chain reaction were mostly consistent with the results of microarray. Cytokine analysis demonstrated that IL-27 and CXCL12 concentrations in responders were significantly higher than non-responders on the 3<sup>rd</sup> day after the first dose and 7<sup>th</sup> day after the second dose of vaccination, respectively. No significant difference was observed in other cytokine and chemokine signatures between the two groups. In conclusion, our results revealed characteristic transcriptome and cytokine changes in hepatitis B vaccine non-responders after boost immunization.


systematic_name: M40970
exact_source: Supplementary Fig 13
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/bin/NIHMS540680-supplement-13.jpg
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with antibody response in peripheral blood mononuclear cell in adults (18-45) after exposure to Menomune A/C/Y/W-135 , time point 3D

description_full:
[cell repeats an earlier one in this file: 1137 characters]


systematic_name: M40971
exact_source: Supplementary Fig 13
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/bin/NIHMS540680-supplement-13.jpg
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with antibody response in peripheral blood mononuclear cell in adults (18-45) (anti-polysaccharide antibody-correlation profile) after exposure to Menactra , time point 3D

description_full:
[cell repeats an earlier one in this file: 1137 characters]


systematic_name: M40972
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700883/table/tab2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell low responders vs high responders in adults (18-55) after exposure to Modified Vaccinia Ankara (MVA) virus vaccine vector , time point 2D. Comment: Enriched for GO terms associated with regulation of T-cell activation and co-stimulation signal (DAVID, fdr<0.05), from 176 DE genes

description_full:
[cell repeats an earlier one in this file: 1940 characters]


systematic_name: M40973
exact_source: Fig 2A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/figure/F2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 7d vs 0d in adults (18-50) after exposure to FluMist , time point 7D. Comment: Molecular signature induced by LAIV vaccination. (a) Interferon (IFN)-related genes differentially expressed after LAIV vaccination

description_full:
  Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons. We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). TIV induced higher antibody titers and more plasmablasts than LAIV did. In subjects vaccinated with TIV, early molecular signatures correlated with and could be used to accurately predict later antibody titers in two independent trials. Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-specific antibody titers, which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses. Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.


systematic_name: M40974
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061512/table/T2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood vaccinated vs candin placebo in infants (4-6m) (BCG-primed) after exposure to Modified Vaccinia Ankara (MVA) virus vaccine vector , time point 1D

description_full:
  BACKGROUND: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. METHODS: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-gamma ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. RESULTS: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-gamma ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. CONCLUSION: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. TRIAL: ClinicalTrials.gov number NCT00953927.


systematic_name: M40975
exact_source: Fig 6A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151076/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in skin of body VZV challenged post-vaccination vs unchallenged in adults (70-93) (VZV challenge) after exposure to Zostavax , time point 72H. Comment: Table showing the top 30 genes upregulated at 72 hours after varicella zoster virus (VZV) challenge before and after vaccination.

description_full:
  Background: The live attenuated vaccine Zostavax was developed to prevent varicella zoster virus (VZV) reactivation that causes herpes zoster (shingles) in older humans. However, the impact of vaccination on the cutaneous response to VZV is not known. Methods: We investigated the response to intradermal VZV antigen challenge before and after Zostavax vaccination in participants > 70 years of age by immunohistological and transcriptomic analyses of skin biopsy specimens collected from the challenge site. Results: Vaccination increased the proportion of VZV-specific CD4+ T cells in the blood and promoted the accumulation of both CD4+ and CD8+ T cells in the skin after VZV antigen challenge. However, Zostavax did not alter the proportion of resident memory T cells (CD4+ and CD8+) or CD4+Foxp3+ regulatory T cells in unchallenged skin. After vaccination, there was increased cutaneous T-cell proliferation at the challenge site and also increased recruitment of T cells from the blood, as indicated by an elevated T-cell migratory gene signature. CD8+ T-cell-associated functional genes were also highly induced in the skin after vaccination. Conclusion: Zostavax vaccination does not alter the abundance of cutaneous resident memory T cells but instead increases the recruitment of VZV-specific T cells from the blood and enhances T-cell activation, particularly cells of the CD8+ subset, in the skin after VZV antigen challenge.


systematic_name: M40976
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151076/bin/jiy420_suppl_supplementary_table_2.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in skin of body 6hr vs 0hr in adults (70-93) (VZV challenge) after exposure to Zostavax , time point 6H. Comment: A List of the top 30 genes upregulated at 6 hours post VZV challenge

description_full:
  Background: The live attenuated vaccine Zostavax was developed to prevent varicella zoster virus (VZV) reactivation that causes herpes zoster (shingles) in older humans. However, the impact of vaccination on the cutaneous response to VZV is not known. Methods: We investigated the response to intradermal VZV antigen challenge before and after Zostavax vaccination in participants > 70 years of age by immunohistological and transcriptomic analyses of skin biopsy specimens collected from the challenge site. Results: Vaccination increased the proportion of VZV-specific CD4+ T cells in the blood and promoted the accumulation of both CD4+ and CD8+ T cells in the skin after VZV antigen challenge. However, Zostavax did not alter the proportion of resident memory T cells (CD4+ and CD8+) or CD4+Foxp3+ regulatory T cells in unchallenged skin. After vaccination, there was increased cutaneous T-cell proliferation at the challenge site and also increased recruitment of T cells from the blood, as indicated by an elevated T-cell migratory gene signature. CD8+ T-cell-associated functional genes were also highly induced in the skin after vaccination. Conclusion: Zostavax vaccination does not alter the abundance of cutaneous resident memory T cells but instead increases the recruitment of VZV-specific T cells from the blood and enhances T-cell activation, particularly cells of the CD8+ subset, in the skin after VZV antigen challenge.


systematic_name: M40977
exact_source: Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723701/table/T1/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in adults (18-40) after exposure to Dryvax , time point 1 to 48M. Comment: top differentially expressed genes, more avail in Suppl Materials

description_full:
  Despite its eradication over 30 years ago, smallpox (as well as other orthopox viruses) remains a pathogen of interest both in terms of biodefense and for its use as a vector for vaccines and immunotherapies. Here we describe the application of mRNA-Seq transcriptome profiling to understanding immune responses in smallpox vaccine recipients. Contrary to other studies examining gene expression in virally infected cell lines, we utilized a mixed population of peripheral blood mononuclear cells in order to capture the essential intercellular interactions that occur in vivo, and would otherwise be lost, using single cell lines or isolated primary cell subsets. In this mixed cell population we were able to detect expression of all annotated vaccinia genes. On the host side, a number of genes encoding cytokines, chemokines, complement factors and intracellular signaling molecules were downregulated upon viral infection, whereas genes encoding histone proteins and the interferon response were upregulated. We also identified a small number of genes that exhibited significantly different expression profiles in subjects with robust humoral immunity compared with those with weaker humoral responses. Our results provide evidence that differential gene regulation patterns may be at work in individuals with robust humoral immunity compared with those with weaker humoral immune responses.


systematic_name: M40978
exact_source: Suppl Fig 2A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072604/bin/ppat.1005892.s008.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with T cell responses (expansion and contraction, not long term) in peripheral blood mononuclear cell in seniors (50-75) after exposure to Zostavax , time point 1D. Comment: (A) Network of genes for which the change in expression correlated with both expansion and contraction and therefore not with long-term outcome

description_full:
[cell repeats an earlier one in this file: 1196 characters]


systematic_name: M40979
exact_source: Supplementary Table 2a: LAIV-Bcells
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-3.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in B cell 7d vs 0d in young adults (18-50) after exposure to FluMist , time point 7D

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M40980
exact_source: Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551876/table/T3/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 24h vs 0h in adults (18-45) (non-responders (previously immunized)) after exposure to Live attenuated vaccine TC-83 , time point 24H. Comment: initial exposure 2-10 months before PBMCs drawn. significant genes chosen for membership in canonical pathways

description_full:
  Venezuelan equine encephalitis virus (VEEV) is a positive-strand RNA Alphavirus endemic in Central and South America, and the causative agent of fatal encephalitis in humans. In an effort to better understand the mechanisms of infection, including differences between people who produce a neutralizing antibody response to the vaccine and those who do not, we performed whole genome transcriptional analysis in human PBMCs exposed in vitro to the live-attenuated vaccine strain of VEEV, TC-83. We compared the molecular responses in cells from three groups of individuals: naive; previously vaccinated individuals who developed a neutralizing antibody response to the vaccine (responders); and those who did not develop a neutralizing antibody response to the vaccine (nonresponders). Overall, the changes in gene expression were more intense for the naive group after TC-83 challenge and least potent in the nonresponder group. The main canonical pathways revealed the involvement of interferon and interferon-induced pathways, as well as toll-like receptors TLR- and interleukin (IL)-12-related pathways. HLA class II genotype and suppression of transcript expression for TLR2, TLR4 and TLR8 in the nonresponder group may help explain the lack of vaccine response in this study group. Because TL3 and TLR7 transcripts were elevated in all study groups, these factors may be indicators of the infection and not the immunological state of the individuals. Biomarkers were identified that differentiate between the vaccine responder and the vaccine nonresponder groups. The identified biomarkers were contrasted against transcripts that were unique to the naive population alone upon induction with TC-83. Biomarker analysis allowed for the discernment between the naive (innate) responses; the responder (recall) responses; and the nonresponder (alternative) changes to gene transcription that were caused by infection with TC-83. The study also points to the existence of HLA haplotypes that may discriminate between vaccine low- and high-responder phenotypes.


systematic_name: M40981
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067885/bin/khvi-14-07-1450122-s001.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell non-responders vs responders in adults (<50) after exposure to Heptatitis B surface antigen vaccine (HBsAg) , time point 28D

description_full:
[cell repeats an earlier one in this file: 1976 characters]


systematic_name: M40982
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067885/bin/khvi-14-07-1450122-s001.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell non-responders vs responders in adults (<50) after exposure to Heptatitis B surface antigen vaccine (HBsAg) , time point 35D

description_full:
[cell repeats an earlier one in this file: 1976 characters]


systematic_name: M40983
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092249/bin/supp_jiu079_jiu079supp_table1.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood 7d vs 0d in children (0.5-14y) after exposure to Fluzone , time point 7D. Comment: ~80% of cohort were white, ~50/50 Female:male

description_full:
  BACKGROUND: Live attenuated influenza vaccine (LAIV) and trivalent inactivated influenza vaccine (TIV) are effective for prevention of influenza virus infection in children, but the mechanisms associated with protection are not well defined. METHODS: We analyzed the differences in B-cell responses and transcriptional profiles in children aged 6 months to 14 years immunized with these 2 vaccines. RESULTS: LAIV elicited a significant increase in naive, memory, and transitional B cells on day 30 after vaccination, whereas TIV elicited an increased number of plasmablasts on day 7. Antibody titers against the 3 vaccine strains (H1N1, H3N2, and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Both vaccines induced overexpression of interferon (IFN)-signaling genes but with different kinetics. TIV induced expression of IFN genes on day 1 after vaccination in all age groups, and LAIV induced expression of IFN genes on day 7 after vaccination but only in children < 5 years old. IFN-related genes overexpressed in both vaccinated groups correlated with H3N2 antibody titers. CONCLUSIONS: These results suggest that LAIV and TIV induced significantly different B-cell responses in vaccinated children. Early induction of IFN appears to be important for development of antibody responses.


systematic_name: M40984
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067885/bin/khvi-14-07-1450122-s001.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell non-responders vs responders in adults (<50) after exposure to Heptatitis B surface antigen vaccine (HBsAg) , time point 7D

description_full:
[cell repeats an earlier one in this file: 1976 characters]


systematic_name: M40985
exact_source: Supplemental Document 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605227/bin/jem.20082292_1.pdf
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 60d vs 0d in unknown after exposure to YF-Vax/Stamaril , time point 60D

description_full:
  Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system.


systematic_name: M40986
exact_source: Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068032/table/tbl1/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with titer response index in peripheral blood mononuclear cell in Caucasian male adults (18-40) (low responders) after exposure to Fluarix/Fluvirin , time point 1D. Comment: Signature predictive of titer response index (TRI). Day 1 and day 3 values averaged.

description_full:
  BACKGROUND: Annual vaccination is the primary means for preventing influenza. However, great interindividual variability exists in vaccine responses, the cellular events that take place in vivo after vaccination are poorly understood, and appropriate biomarkers for vaccine responsiveness have not been developed. METHODS: We immunized a cohort of healthy male adults with a licensed trivalent influenza vaccine and performed a timed assessment of global gene expression before and after vaccination. We analyzed the relationship between gene expression patterns and the humoral immune response to vaccination. RESULTS: Marked up regulation of expression of genes involved in interferon signaling, positive IL-6 regulation, and antigen processing and presentation, were detected within 24 hours of immunization. The late vaccine response showed a transcriptional pattern suggestive of increased protein biosynthesis and cellular proliferation. Integrative analyses revealed a 494-gene expression signature--including STAT1, CD74, and E2F2--which strongly correlates with the magnitude of the antibody response. High vaccine responder status correlates with increased early expression of interferon signaling and antigen processing and presentation genes. CONCLUSIONS: The results highlight the role of a systems biology approach in understanding the molecular events that take place in vivo after influenza vaccination and in the development of better predictors of vaccine responsiveness.


systematic_name: M40987
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133148/table/T2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 28d vs 3d in adults (50-74) (in common with both HAI and VNA) after exposure to Fluarix , time point 28D , administered i.m.. Comment: Common Genesets with genes entering regression models for HAI and VNA Responses, withlog2 Day 28 vs Day 3 fold-change in gene expression as the explanatory variables

description_full:
  This study aimed to identify gene expression markers shared between both influenza hemagglutination inhibition (HAI) and virus-neutralization antibody (VNA) responses. We enrolled 158 older subjects who received the 2010-2011 trivalent inactivated influenza vaccine. Influenza-specific HAI and VNA titers and mRNA-sequencing were performed using blood samples obtained at Days 0, 3 and 28 post vaccination. For antibody response at Day 28 versus Day 0, several gene sets were identified as significant in predictive models for HAI (n=7) and VNA (n=35) responses. Five gene sets (comprising the genes MAZ, TTF, GSTM, RABGGTA, SMS, CA, IFNG and DOPEY) were in common for both HAI and VNA. For response at Day 28 versus Day 3, many gene sets were identified in predictive models for HAI (n=13) and VNA (n=41). Ten gene sets (comprising biologically related genes, such as MAN1B1, POLL, CEBPG, FOXP3, IL12A, TLR3, TLR7 and others) were shared between HAI and VNA. These identified gene sets demonstrated a high degree of network interactions and likelihood for functional relationships. Influenza-specific HAI and VNA responses demonstrated a remarkable degree of similarity. Although unique gene set signatures were identified for each humoral outcome, several gene sets were determined to be in common with both HAI and VNA response to influenza vaccine.


systematic_name: M40988
exact_source: Suppl Fig 2B
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072604/bin/ppat.1005892.s008.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with T cell responses (long term) in peripheral blood mononuclear cell in seniors (50-75) after exposure to Zostavax , time point 1D. Comment: (B) Network of genes informative of long-term responses.

description_full:
[cell repeats an earlier one in this file: 1196 characters]


systematic_name: M40989
exact_source: s4_nkc_d28
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in natural killer cell 28d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 28D , administered i.m.

description_full:
  BACKGROUND: Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. OBJECTIVE: We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18-49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. RESULTS: Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. CONCLUSIONS: Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. TRIAL: ClinicalTrials.gov NCT01573312.


systematic_name: M40990
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061512/table/T2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood vaccinated vs candin placebo in infants (4-6m) (BCG-primed) after exposure to Modified Vaccinia Ankara (MVA) virus vaccine vector , time point 1D

description_full:
  BACKGROUND: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. METHODS: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-gamma ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. RESULTS: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-gamma ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. CONCLUSION: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. TRIAL: ClinicalTrials.gov number NCT00953927.


systematic_name: M40991
exact_source: Suppl Table 5
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-6.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with HAI response at 28d in peripheral blood mononuclear cell in adults (18-50) after exposure to Fluarix/Fluvirin , time point 7D. Comment: Supplementary Table 5: All genes whose expression (d3/d0 or d7/d0) correlates to the fold increase in HAI titers (d28/d0).

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M40992
exact_source: s4_neu_d3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in neutrophil 3d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 3D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 1986 characters]


systematic_name: M40993
exact_source: Suppl File 1, Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713456/bin/elife-00299-supp1.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with antibody response in blood in adults (18-40) after exposure to Sanofi Pasteur, SA, Inactivated influenza vaccine , time point 1D

description_full:
  Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy. We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine. We identified 20 genes exhibiting a transcriptional response to vaccination, significant genotype effects on gene expression, and correlation between the transcriptional and antibody responses. The results show that variation at the level of genes involved in membrane trafficking and antigen processing significantly influences the human response to influenza vaccination. More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits. DOI:http://dx.doi.org/10.7554/eLife.00299.001.


systematic_name: M40994
exact_source: Fig 6A (ID)
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832504/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in CD4-positive, alpha-beta memory T cell 7d vs 0d in adults (18-45) after exposure to BCG vaccine , time point 7D , administered ID (intradermal). Comment: top 100 most significantly altered genes comparing Day 0 and Day 7 responses directly ex vivo

description_full:
  Protective efficacy of Bacillus Calmette-Guerin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-gamma production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4<sup>+</sup> memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.


systematic_name: M40995
exact_source: s4_mnc_d1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in monocyte 1d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 1D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 1986 characters]


systematic_name: M40996
exact_source: s4_neu_d1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in neutrophil 1d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 1D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 1986 characters]


systematic_name: M40997
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500554/bin/jiy721_suppl_supplementary_table_1a.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell vaccinated with AS03 adjuvant vs phosphate-bufferred saline in adults (19-39) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 1D , administered i.m.

description_full:
  BACKGROUND: Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood. METHODS: Using ribonucleic acid sequencing on peripheral blood mononuclear cells (PBMCs) from AS03-adjuvanted and unadjuvanted inactivated H5N1 vaccine recipients, we identified differentially expressed genes, enriched pathways, and genes that correlated with serologic responses. We compared bulk PBMC findings with our previously published assessments of flow-sorted immune cell types. RESULTS: AS03-adjuvanted vaccine induced the strongest differential signals on day 1 postvaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, Fcgamma receptor (FcgammaR)-mediated phagocytosis, and antigen processing and presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared with individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMCs, and several pathways identified in individual cell types were absent in PBMCs. CONCLUSIONS: Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5- to 8-fold upregulation of Fc-gammaR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. Although PBMCs and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.


systematic_name: M40998
exact_source: s4_dnc_d1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in dendritic cell 1d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 1D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 1986 characters]


systematic_name: M40999
exact_source: Fig 4
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/figure/F4/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-45) after exposure to Menactra , time point 7D

description_full:
[cell repeats an earlier one in this file: 1137 characters]


systematic_name: M41000
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in neutrophil 3d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 3D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41001
exact_source: Supplemental Document 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605227/bin/jem.20082292_1.pdf
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 60d vs 0d in unknown after exposure to YF-Vax/Stamaril , time point 60D

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41002
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151076/bin/jiy420_suppl_supplementary_table_1.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in skin of body 6hr vs 0hr in adults (70-93) (VZV challenge) after exposure to Zostavax , time point 6H

description_full:
[cell repeats an earlier one in this file: 1437 characters]


systematic_name: M41003
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834766/bin/Table_2.XLSX
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood 6hr vs 0hr in adults (18-45) after exposure to CN54gp140 adjuvanted with GLA-AF , time point 6H , administered i.m.

description_full:
  Systems biology approaches have recently provided new insights into the mechanisms of action of human vaccines and adjuvants. Here, we investigated early transcriptional signatures induced in whole blood of healthy subjects following vaccination with a recombinant HIV-1 envelope glycoprotein subunit CN54gp140 adjuvanted with the TLR4 agonist glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) and correlated signatures to CN54gp140-specific serum antibody responses. Fourteen healthy volunteers aged 18-45 years were immunized intramuscularly three times at 1-month intervals and whole blood samples were collected at baseline, 6 h, and 1, 3, and 7 days post first immunization. Subtle changes in the transcriptomic profiles were observed following immunization, ranging from over 300 differentially expressed genes (DEGs) at day 1 to nearly 100 DEGs at day 7 following immunization. Functional pathway analysis revealed blood transcription modules (BTMs) related to general cell cycle activation, and innate immune cell activation at early time points, as well as BTMs related to T cells and B cell activation at the later time points post-immunization. Diverse CN54gp140-specific serum antibody responses of the subjects enabled their categorization into high or low responders, at early ( < 1 month) and late (up to 6 months) time points post vaccination. BTM analyses revealed repression of modules enriched in NK cells, and the mitochondrial electron chain, in individuals with high or sustained antigen-specific antibody responses. However, low responders showed an enhancement of BTMs associated with enrichment in myeloid cells and monocytes as well as integrin cell surface interactions. Flow cytometry analysis of peripheral blood mononuclear cells obtained from the subjects revealed an enhanced frequency of CD56<sup>dim</sup> NK cells in the majority of vaccines 14 days after vaccination as compared with the baseline. These results emphasize the utility of a systems biology approach to enhance our understanding on the mechanisms of action of TLR4 adjuvanted human vaccines.


systematic_name: M41004
exact_source: Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061512/table/T3/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 28d vs 7d in infants (4-6m) (BCG-primed) after exposure to Modified Vaccinia Ankara (MVA) virus vaccine vector , time point 28D

description_full:
  BACKGROUND: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. METHODS: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-gamma ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. RESULTS: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-gamma ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. CONCLUSION: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. TRIAL: ClinicalTrials.gov number NCT00953927.


systematic_name: M41005
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834766/bin/Table_2.XLSX
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood 3d vs 0hr in adults (18-45) after exposure to CN54gp140 adjuvanted with GLA-AF , time point 3D , administered i.m.

description_full:
  Systems biology approaches have recently provided new insights into the mechanisms of action of human vaccines and adjuvants. Here, we investigated early transcriptional signatures induced in whole blood of healthy subjects following vaccination with a recombinant HIV-1 envelope glycoprotein subunit CN54gp140 adjuvanted with the TLR4 agonist glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) and correlated signatures to CN54gp140-specific serum antibody responses. Fourteen healthy volunteers aged 18-45 years were immunized intramuscularly three times at 1-month intervals and whole blood samples were collected at baseline, 6 h, and 1, 3, and 7 days post first immunization. Subtle changes in the transcriptomic profiles were observed following immunization, ranging from over 300 differentially expressed genes (DEGs) at day 1 to nearly 100 DEGs at day 7 following immunization. Functional pathway analysis revealed blood transcription modules (BTMs) related to general cell cycle activation, and innate immune cell activation at early time points, as well as BTMs related to T cells and B cell activation at the later time points post-immunization. Diverse CN54gp140-specific serum antibody responses of the subjects enabled their categorization into high or low responders, at early ( < 1 month) and late (up to 6 months) time points post vaccination. BTM analyses revealed repression of modules enriched in NK cells, and the mitochondrial electron chain, in individuals with high or sustained antigen-specific antibody responses. However, low responders showed an enhancement of BTMs associated with enrichment in myeloid cells and monocytes as well as integrin cell surface interactions. Flow cytometry analysis of peripheral blood mononuclear cells obtained from the subjects revealed an enhanced frequency of CD56<sup>dim</sup> NK cells in the majority of vaccines 14 days after vaccination as compared with the baseline. These results emphasize the utility of a systems biology approach to enhance our understanding on the mechanisms of action of TLR4 adjuvanted human vaccines.


systematic_name: M41006
exact_source: Suppl Table 1B, Tab DEGs_LAIV
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-2.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 7d vs 0d in adults (18-50) after exposure to Fluarix/Fluvirin , time point 7D. Comment: Supplementary Table 1b: All the differentially expressed genes identified in PBMCs of TIV vaccinees.

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41007
exact_source: Fig 5e
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485475/figure/F5/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 1d vs 0d in adults (18-64) (medium-high adverse events score) after exposure to Pandemrix , time point 1D

description_full:
  Adjuvanted vaccines afford invaluable protection against disease, and the molecular and cellular changes they induce offer direct insight into human immunobiology. Here we show that within 24 h of receiving adjuvanted swine flu vaccine, healthy individuals made expansive, complex molecular and cellular responses that included overt lymphoid as well as myeloid contributions. Unexpectedly, this early response was subtly but significantly different in people older than ~35 years. Wide-ranging adverse clinical events can seriously confound vaccine adoption, but whether there are immunological correlates of these is unknown. Here we identify a molecular signature of adverse events that was commonly associated with an existing B cell phenotype. Thus immunophenotypic variation among healthy humans may be manifest in complex pathophysiological responses.


systematic_name: M41008
exact_source: Suppl Table 1B, Tab DEGs_LAIV
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-2.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-50) after exposure to FluMist , time point 3D. Comment: Supplementary Table 1b: All the differentially expressed genes identified in PBMCs of TIV vaccinees.

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41009
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in myeloid dendritic cell 7d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 7D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41010
exact_source: s4_neu_d1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in neutrophil 1d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 1D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 1986 characters]


systematic_name: M41011
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485475/bin/NIHMS65741-supplement-2.pdf
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with age in peripheral blood mononuclear cell in adults (18-64) after exposure to Pandemrix , time point 1D

description_full:
  Adjuvanted vaccines afford invaluable protection against disease, and the molecular and cellular changes they induce offer direct insight into human immunobiology. Here we show that within 24 h of receiving adjuvanted swine flu vaccine, healthy individuals made expansive, complex molecular and cellular responses that included overt lymphoid as well as myeloid contributions. Unexpectedly, this early response was subtly but significantly different in people older than ~35 years. Wide-ranging adverse clinical events can seriously confound vaccine adoption, but whether there are immunological correlates of these is unknown. Here we identify a molecular signature of adverse events that was commonly associated with an existing B cell phenotype. Thus immunophenotypic variation among healthy humans may be manifest in complex pathophysiological responses.


systematic_name: M41012
exact_source: Fig S7b
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763735/figure/sfig07/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with HAI response in peripheral blood mononuclear cell in children (14-27m) (MF59-adjuvanted and non-adjuvanted) after exposure to Fluad/Imuvac , time point 1D. Comment: Genes in BTM M75

description_full:
[cell repeats an earlier one in this file: 1291 characters]


systematic_name: M41013
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in neutrophil 1d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 1D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41014
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in natural killer cell 7d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 7D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41015
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 3d vs 0d in adults after exposure to Inactivated influenza vaccine , time point 3D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41016
exact_source: Suppl. Fig 8
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485475/bin/NIHMS65741-supplement-1.pdf
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell -7d vs 0d in adults (18-64) (low AE subjects vs medium/high AE subjects) after exposure to Pandemrix (A/California/7/09 (H1N1)) , time point 0D

description_full:
  Adjuvanted vaccines afford invaluable protection against disease, and the molecular and cellular changes they induce offer direct insight into human immunobiology. Here we show that within 24 h of receiving adjuvanted swine flu vaccine, healthy individuals made expansive, complex molecular and cellular responses that included overt lymphoid as well as myeloid contributions. Unexpectedly, this early response was subtly but significantly different in people older than ~35 years. Wide-ranging adverse clinical events can seriously confound vaccine adoption, but whether there are immunological correlates of these is unknown. Here we identify a molecular signature of adverse events that was commonly associated with an existing B cell phenotype. Thus immunophenotypic variation among healthy humans may be manifest in complex pathophysiological responses.


systematic_name: M41017
exact_source: Fig 4D
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729923/figure/f4/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood responders vs poor responders in seniors (65-81) (responders (training set)) after exposure to Twinrix , time point 0D. Comment: Network inference based on the 15 markers identified as predictors of the response to the HBV vaccine.

description_full:
  Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear. In this study hepatitis B virus (HBV)-naive older adults received three vaccines, including one against HBV. Here we show, using transcriptional and cytometric profiling of whole blood collected before vaccination, that heightened expression of genes that augment B-cell responses and higher memory B-cell frequencies correlate with stronger responses to HBV vaccine. In contrast, higher levels of inflammatory response transcripts and increased frequencies of pro-inflammatory innate cells correlate with weaker responses to this vaccine. Increased numbers of erythrocytes and the haem-induced response also correlate with poor response to the HBV vaccine. A transcriptomics-based pre-vaccination predictor of response to HBV vaccine is built and validated in distinct sets of older adults. This moderately accurate (area under the curve ~65%) but robust signature is supported by flow cytometry and cytokine profiling. This study is the first that identifies baseline predictors and mechanisms of response to the HBV vaccine.


systematic_name: M41018
exact_source: Supplementary Table 2a: LAIV-pDC
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-3.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in plasmacytoid dendritic cell 7d vs 0d in young adults (18-50) after exposure to FluMist , time point 7D

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41019
exact_source: Suppl Table 5
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-6.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with HAI response at 28d in peripheral blood mononuclear cell in adults (18-50) after exposure to Fluarix/Fluvirin , time point 3D. Comment: Supplementary Table 5: All genes whose expression (d3/d0 or d7/d0) correlates to the fold increase in HAI titers (d28/d0).

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41020
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in myeloid dendritic cell 1d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 1D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41021
exact_source: Fig S2C
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338562/figure/sfig02/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell immunized with ARR vs immunized by RRR in unknown (primary immunization with recombinant adenovirus 35 (Ad35)) after exposure to P. falciparum RTS,S/AS01 , time point 1D

description_full:
  RTS,S is an advanced malaria vaccine candidate and confers significant protection against <i>Plasmodium falciparum</i> infection in humans. Little is known about the molecular mechanisms driving vaccine immunity. Here, we applied a systems biology approach to study immune responses in subjects receiving three consecutive immunizations with RTS,S (RRR), or in those receiving two immunizations of RTS,S/AS01 following a primary immunization with adenovirus 35 (Ad35) (ARR) vector expressing circumsporozoite protein. Subsequent controlled human malaria challenge (CHMI) of the vaccinees with <i>Plasmodium</i>-infected mosquitoes, 3 wk after the final immunization, resulted in ~50% protection in both groups of vaccinees. Circumsporozoite protein (CSP)-specific antibody titers, prechallenge, were associated with protection in the RRR group. In contrast, ARR-induced lower antibody responses, and protection was associated with polyfunctional CD4<sup>+</sup> T-cell responses 2 wk after priming with Ad35. Molecular signatures of B and plasma cells detected in PBMCs were highly correlated with antibody titers prechallenge and protection in the RRR cohort. In contrast, early signatures of innate immunity and dendritic cell activation were highly associated with protection in the ARR cohort. For both vaccine regimens, natural killer (NK) cell signatures negatively correlated with and predicted protection. These results suggest that protective immunity against <i>P. falciparum</i> can be achieved via multiple mechanisms and highlight the utility of systems approaches in defining molecular correlates of protection to vaccination.


systematic_name: M41022
exact_source: Suppl mat, 2016HV0244R-s01.xlsx
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287313/bin/khvi-13-01-1227900-s001.zip
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood vaccinated vs control in adults (23-48) after exposure to Live attenuated vaccine TC-83 , time point 14D

description_full:
  Venezuelan equine encephalitis virus (VEEV) is an important human and animal alphavirus pathogen transmitted by mosquitoes. The virus is endemic in Central and South America, but has also caused equine outbreaks in southwestern areas of the United States. In an effort to better understand the molecular mechanisms of the development of immunity to this important pathogen, we performed transcriptional analysis from whole, unfractionated human blood of patients who had been immunized with the live-attenuated vaccine strain of VEEV, TC-83. We compared changes in the transcriptome between naive individuals who were mock vaccinated with saline to responses of individuals who received TC-83. Significant transcriptional changes were noted at days 2, 7, and 14 following vaccination. The top canonical pathways revealed at early and intermediate time points (days 2 and 7) included the involvement of the classic interferon response, interferon-response factors, activation of pattern recognition receptors, and engagement of the inflammasome. By day 14, the top canonical pathways included oxidative phosphorylation, the protein ubiquitination pathway, natural killer cell signaling, and B-cell development. Biomarkers were identified that differentiate between vaccinees and control subjects, at early, intermediate, and late stages of the development of immunity as well as markers which were common to all 3 stages following vaccination but distinct from the sham-vaccinated control subjects. The study represents a novel examination of molecular processes that lead to the development of immunity against VEEV in humans and which may be of value as diagnostic targets, to enhance modern vaccine design, or molecular correlates of protection.


systematic_name: M41023
exact_source: Suppl mat, 2016HV0244R-s01.xlsx
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287313/bin/khvi-13-01-1227900-s001.zip
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood vaccinated vs control in adults (23-48) after exposure to Live attenuated vaccine TC-83 , time point 7D

description_full:
  Venezuelan equine encephalitis virus (VEEV) is an important human and animal alphavirus pathogen transmitted by mosquitoes. The virus is endemic in Central and South America, but has also caused equine outbreaks in southwestern areas of the United States. In an effort to better understand the molecular mechanisms of the development of immunity to this important pathogen, we performed transcriptional analysis from whole, unfractionated human blood of patients who had been immunized with the live-attenuated vaccine strain of VEEV, TC-83. We compared changes in the transcriptome between naive individuals who were mock vaccinated with saline to responses of individuals who received TC-83. Significant transcriptional changes were noted at days 2, 7, and 14 following vaccination. The top canonical pathways revealed at early and intermediate time points (days 2 and 7) included the involvement of the classic interferon response, interferon-response factors, activation of pattern recognition receptors, and engagement of the inflammasome. By day 14, the top canonical pathways included oxidative phosphorylation, the protein ubiquitination pathway, natural killer cell signaling, and B-cell development. Biomarkers were identified that differentiate between vaccinees and control subjects, at early, intermediate, and late stages of the development of immunity as well as markers which were common to all 3 stages following vaccination but distinct from the sham-vaccinated control subjects. The study represents a novel examination of molecular processes that lead to the development of immunity against VEEV in humans and which may be of value as diagnostic targets, to enhance modern vaccine design, or molecular correlates of protection.


systematic_name: M41024
exact_source: s4_tcl_d1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in T cell 1d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 1D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 1986 characters]


systematic_name: M41025
exact_source: Suppl Table IV
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701477/bin/NIHMS83712-supplement-Suplementary_t.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in young adults (18-25) after exposure to HPV-16 L1 VLP , time point 0D. Comment: List of Genes induced by VLP directly, independently of vaccination (p<0.05 and FC>1.30)

description_full:
[cell repeats an earlier one in this file: 1766 characters]


systematic_name: M41026
exact_source: Fig 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711596/figure/F1/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood 7d vs 0d in children (3-17) after exposure to Flumist Quadrivalent (LAIV) , time point 7D. Comment: LAIV (live attenuated influenza vaccine)

description_full:
  BACKGROUND: In recent influenza seasons, the live attenuated influenza vaccine (LAIV) has not demonstrated the same level of vaccine effectiveness as that observed among children who received the inactivated influenza vaccine (IIV). To better understand this difference, this study compared the mRNA sequencing transcription profile (RNA seq) in children who received either IIV or LAIV. METHODS: Children 3-17years of age receiving quadrivalent influenza vaccine were enrolled. Blood samples were collected on Day 0 prior to vaccination and again on Day 7 (range 6-10days) following vaccination. Total RNA was isolated from PAXgene tubes and sequenced for a custom panel of 89 transcripts using the TruSeq Targeted RNA Expression method. Fold differences in normalized RNA seq counts from Day 0 to Day 7 were calculated, log<sub>2</sub> transformed and compared between the two vaccine groups. RESULTS: Of 72 children, 46 received IIV and 26 received LAIV. Following IIV vaccination, 7 genes demonstrated significant differential expression at Day 7 (down-regulated). In contrast, following LAIV vaccination, 8 genes demonstrated significant differential expression at Day 7 (5 up-regulated and 3 down-regulated). Only two genes demonstrated similar patterns of regulation in both groups. CONCLUSIONS: Differential regulation of genes was observed between 2015-16 LAIV and IIV recipients. These results help to elucidate the immune response to influenza vaccines and may be related to the difference in vaccine effectiveness observed in recent years between LAIV and IIV.


systematic_name: M41027
exact_source: Results: Modulation of gene expression by HIV-LIPO-5
external_details_URL: https://www.ncbi.nlm.nih.gov/pubmed/?term=23759749
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in adults (37-48) after exposure to HIV-LIPO-5 , time point 14W. Comment: genes with a significant variation at W14 after 24-h HIV-LIPO-5 stimulation, IFN-gamma, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6 were overexpressed with a fold change |FC| >1.8

description_full:
  OBJECTIVE: To dissect the biological mechanisms involved in the cellular responses to a candidate vaccine containing 5 HIV peptides coupled to a palmytoil tail (HIV-LIPO-5) in healthy volunteers, by using extensive immunogenicity assessments with different stimulation durations. DESIGN: Immunogenicity substudy of a randomized phase II prophylactic HIV vaccine trial (ANRS VAC 18). METHODS: HIV-LIPO-5 or placebo was administered at W0, W4, W12 and W24. Peripheral blood mononuclear cells from a subset of participants at W0 and W14 were stimulated with HIV-LIPO-5, Gag peptides contained in the vaccine and control peptides. ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses were performed. Different time points and stimulation conditions were compared, controlling for test multiplicity. RESULTS: Cultured ELISpot and lymphoproliferation responses were detected at W14. Ex-vivo ICS showed mainly interleukin (IL)-2-producing cells. Secretion of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, IL-5 and IL-13 increased significantly after culture and Gag stimulation at W14 compared to W0. Metallothionein genes were consistently overexpressed after HIV-LIPO-5 stimulation at W0 and W14. At W14, significant probes increased substantially, including IFN-gamma, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6. Canonical pathway analyses indicated a role of interferon signalling genes in response to HIV-LIPO-5. CONCLUSION: HIV-LIPO-5 vaccination elicited Th1 and Th2 memory precursor responses and a consistent modulation in gene expression. The response profile before vaccination suggests an adjuvant effect of the lipid tail of HIV-LIPO-5. Our combined immunogenicity analyses allowed to identify a specific signature profile of HIV-LIPO-5 and indicate that HIV-LIPO-5 could be further developed as a prime in heterologous prime-boost strategies.


systematic_name: M41028
exact_source: Fig 4B
external_details_URL: https://www.ncbi.nlm.nih.gov/pubmed/?term=23759749
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in adults (37-48) after exposure to HIV-LIPO-5 , time point 14W. Comment: Genes that act in the interferon pathway

description_full:
  OBJECTIVE: To dissect the biological mechanisms involved in the cellular responses to a candidate vaccine containing 5 HIV peptides coupled to a palmytoil tail (HIV-LIPO-5) in healthy volunteers, by using extensive immunogenicity assessments with different stimulation durations. DESIGN: Immunogenicity substudy of a randomized phase II prophylactic HIV vaccine trial (ANRS VAC 18). METHODS: HIV-LIPO-5 or placebo was administered at W0, W4, W12 and W24. Peripheral blood mononuclear cells from a subset of participants at W0 and W14 were stimulated with HIV-LIPO-5, Gag peptides contained in the vaccine and control peptides. ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses were performed. Different time points and stimulation conditions were compared, controlling for test multiplicity. RESULTS: Cultured ELISpot and lymphoproliferation responses were detected at W14. Ex-vivo ICS showed mainly interleukin (IL)-2-producing cells. Secretion of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, IL-5 and IL-13 increased significantly after culture and Gag stimulation at W14 compared to W0. Metallothionein genes were consistently overexpressed after HIV-LIPO-5 stimulation at W0 and W14. At W14, significant probes increased substantially, including IFN-gamma, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6. Canonical pathway analyses indicated a role of interferon signalling genes in response to HIV-LIPO-5. CONCLUSION: HIV-LIPO-5 vaccination elicited Th1 and Th2 memory precursor responses and a consistent modulation in gene expression. The response profile before vaccination suggests an adjuvant effect of the lipid tail of HIV-LIPO-5. Our combined immunogenicity analyses allowed to identify a specific signature profile of HIV-LIPO-5 and indicate that HIV-LIPO-5 could be further developed as a prime in heterologous prime-boost strategies.


systematic_name: M41029
exact_source: Suppl mat, 2016HV0244R-s01.xlsx
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287313/bin/khvi-13-01-1227900-s001.zip
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood vaccinated vs control in adults (23-48) after exposure to Live attenuated vaccine TC-83 , time point 7D

description_full:
[cell repeats an earlier one in this file: 1747 characters]


systematic_name: M41030
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in natural killer cell 1d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 1D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41032
exact_source: Suppl Fig 6a, Fig 4C
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell responders vs nonresponders in adults (18-64) after exposure to Pandemrix , time point 7D

description_full:
[cell repeats an earlier one in this file: 858 characters]

external_details_URL:
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485475/bin/NIHMS65741-supplement-1.pdf| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485475/figure/F4/


systematic_name: M41033
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 1d vs 0d in adults after exposure to Inactivated influenza vaccine , time point 1D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41034
exact_source: Fig 7A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909487/figure/f0035/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with whole blood bactericidal activity in peripheral blood mononuclear cell in adults (18-40) after exposure to Tice BCG/rBCG-Ag85A/Ag85B , time point 14D

description_full:
  BACKGROUND: We report a first-in-human trial evaluating safety and immunogenicity of a recombinant BCG, AERAS-422, over-expressing TB antigens Ag85A, Ag85B, and Rv3407 and expressing mutant perfringolysin. METHODS: This was a randomized, double-blind, dose-escalation trial in HIV-negative, healthy adult, BCG-naÃ¯ve volunteers, negative for prior exposure to Mtb, at one US clinical site. Volunteers were randomized 2:1 at each dose level to receive a single intradermal dose of AERAS-422 ( > 10(5)- < 10(6)CFU=low dose, â‰¥10(6)- < 10(7)CFU=high dose) or non-recombinant Tice BCG (1-8Ã—10(5)CFU). Randomization used an independently prepared randomly generated sequence of treatment assignments. The primary and secondary outcomes were safety and immunogenicity, respectively, assessed in all participants through 182days post-vaccination. ClinicalTrials.gov registration number: NCT01340820. FINDINGS: Between Nov 2010 and Aug 2011, 24 volunteers were enrolled (AERAS-422 high dose, n=8; AERAS-422 low dose, n=8; Tice BCG, n=8); all were included in the safety and immunogenicity analyses. All 24 subjects had at least one adverse event, primarily expected local reactions. High dose AERAS-422 vaccination induced Ag85A- and Ag85B-specific lymphoproliferative responses and marked anti-mycobacterial activity in a whole blood bactericidal activity culture assay (WBA), but was associated with varicella zoster virus (VZV) reactivation in two vaccinees. These volunteers displayed high BCG-specific IFN-Î³ responses pre- and post-vaccination possibly predisposing them to autocrine/paracrine negative regulation of immune control of latent VZV. A systems biology transcriptomal approach identified positive correlations between post-vaccination T cell expression modules and WBA, and negative correlations between post-vaccination monocyte expression modules and WBA. The expression of one key macrophage marker (F4/80) was constitutively elevated in the two volunteers with zoster. INTERPRETATION: The unexpected development of VZV in two of eight healthy adult vaccine recipients resulted in discontinuation of AERAS-422 vaccine development. Immunological and transcriptomal data identified correlations with the development of TB immunity and VZV that require further investigation. FUNDING: Aeras, FDA, Bill and Melinda Gates Foundation.


systematic_name: M41035
exact_source: Suppl Fig 6
external_details_URL: http://links.lww.com/QAD/A314
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in adults (37-48) after exposure to HIV-LIPO-5 , time point 14W. Comment: top functional network of up-regulated genes

description_full:
  OBJECTIVE: To dissect the biological mechanisms involved in the cellular responses to a candidate vaccine containing 5 HIV peptides coupled to a palmytoil tail (HIV-LIPO-5) in healthy volunteers, by using extensive immunogenicity assessments with different stimulation durations. DESIGN: Immunogenicity substudy of a randomized phase II prophylactic HIV vaccine trial (ANRS VAC 18). METHODS: HIV-LIPO-5 or placebo was administered at W0, W4, W12 and W24. Peripheral blood mononuclear cells from a subset of participants at W0 and W14 were stimulated with HIV-LIPO-5, Gag peptides contained in the vaccine and control peptides. ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses were performed. Different time points and stimulation conditions were compared, controlling for test multiplicity. RESULTS: Cultured ELISpot and lymphoproliferation responses were detected at W14. Ex-vivo ICS showed mainly interleukin (IL)-2-producing cells. Secretion of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, IL-5 and IL-13 increased significantly after culture and Gag stimulation at W14 compared to W0. Metallothionein genes were consistently overexpressed after HIV-LIPO-5 stimulation at W0 and W14. At W14, significant probes increased substantially, including IFN-gamma, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6. Canonical pathway analyses indicated a role of interferon signalling genes in response to HIV-LIPO-5. CONCLUSION: HIV-LIPO-5 vaccination elicited Th1 and Th2 memory precursor responses and a consistent modulation in gene expression. The response profile before vaccination suggests an adjuvant effect of the lipid tail of HIV-LIPO-5. Our combined immunogenicity analyses allowed to identify a specific signature profile of HIV-LIPO-5 and indicate that HIV-LIPO-5 could be further developed as a prime in heterologous prime-boost strategies.


systematic_name: M41036
exact_source: Supplementary Fig 13
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/bin/NIHMS540680-supplement-13.jpg
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with antibody response in peripheral blood mononuclear cell in adults (18-45) after exposure to Menomune A/C/Y/W-135 , time point 3D

description_full:
[cell repeats an earlier one in this file: 1137 characters]


systematic_name: M41037
exact_source: Supplementary Fig 13
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/bin/NIHMS540680-supplement-13.jpg
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with antibody response in peripheral blood mononuclear cell in adults (18-45) (anti-DT antibody-correlation profile) after exposure to Menactra , time point 3D

description_full:
[cell repeats an earlier one in this file: 1137 characters]


systematic_name: M41038
exact_source: Supplementary Fig 13
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946932/bin/NIHMS540680-supplement-13.jpg
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with antibody response in peripheral blood mononuclear cell in adults (18-45) (anti-polysaccharide antibody-correlation profile) after exposure to Menactra , time point 3D

description_full:
[cell repeats an earlier one in this file: 1137 characters]


systematic_name: M41039
exact_source: Fig 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711596/figure/F1/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 7d vs 0d in children (3-17) after exposure to Fluzone/Fluarix (IIV) , time point 7D. Comment: IIV (inactivated influenza vaccine)

description_full:
  BACKGROUND: In recent influenza seasons, the live attenuated influenza vaccine (LAIV) has not demonstrated the same level of vaccine effectiveness as that observed among children who received the inactivated influenza vaccine (IIV). To better understand this difference, this study compared the mRNA sequencing transcription profile (RNA seq) in children who received either IIV or LAIV. METHODS: Children 3-17years of age receiving quadrivalent influenza vaccine were enrolled. Blood samples were collected on Day 0 prior to vaccination and again on Day 7 (range 6-10days) following vaccination. Total RNA was isolated from PAXgene tubes and sequenced for a custom panel of 89 transcripts using the TruSeq Targeted RNA Expression method. Fold differences in normalized RNA seq counts from Day 0 to Day 7 were calculated, log<sub>2</sub> transformed and compared between the two vaccine groups. RESULTS: Of 72 children, 46 received IIV and 26 received LAIV. Following IIV vaccination, 7 genes demonstrated significant differential expression at Day 7 (down-regulated). In contrast, following LAIV vaccination, 8 genes demonstrated significant differential expression at Day 7 (5 up-regulated and 3 down-regulated). Only two genes demonstrated similar patterns of regulation in both groups. CONCLUSIONS: Differential regulation of genes was observed between 2015-16 LAIV and IIV recipients. These results help to elucidate the immune response to influenza vaccines and may be related to the difference in vaccine effectiveness observed in recent years between LAIV and IIV.


systematic_name: M41040
exact_source: Suppl File 1, Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713456/bin/elife-00299-supp1.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with antibody response in blood in adults (18-40) after exposure to Sanofi Pasteur, SA, Inactivated influenza vaccine , time point 3D

description_full:
[cell repeats an earlier one in this file: 900 characters]


systematic_name: M41041
exact_source: Additional File 2, Tab A BCG
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654906/bin/1755-8794-2-10-S2.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in infants (10w) after exposure to BCG (Danish strain BCG Statens Serum Institut, Denmark) , time point 10W. Comment: PBMCs drawn at 10 weeks following immunization at birth

description_full:
  BACKGROUND: Novel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guerin (BCG). Because BCG vaccination is used extensively in infants, this population group is likely to be the first in which efficacy trials of new vaccines will be conducted. However, our understanding of the complexity of immunity to BCG in infants is inadequate, making interpretation of vaccine-induced immune responses difficult. METHODS: To better understand BCG-induced immunity, we performed gene expression profiling in five 10-week old infants routinely vaccinated with BCG at birth. RNA was extracted from 12 hour BCG-stimulated or purified protein derivative of tuberculin (PPD)-stimulated PBMC, isolated from neonatal blood collected 10 weeks after vaccination. RNA was hybridised to the Sentrix(R) HumanRef-8 Expression BeadChip (Illumina) to measure expression of > 16,000 genes. RESULTS: We found that ex vivo stimulation of PBMC with PPD and BCG induced largely similar gene expression profiles, except that BCG induced greater macrophage activation. The peroxisome proliferator-activated receptor (PPAR) signaling pathway, including PPAR-gamma, involved in activation of the alternative, anti-inflammatory macrophage response was down-regulated following stimulation with both antigens. In contrast, up-regulation of genes associated with the classic, pro-inflammatory macrophage response was noted. Further analysis revealed a decrease in the expression of cell adhesion molecules (CAMs), including integrin alpha M (ITGAM), which is known to be important for entry of mycobacteria into the macrophage. Interestingly, more leukocyte genes were down-regulated than up-regulated. CONCLUSION: Our results suggest that a combination of suppressed and up-regulated genes may be key in determining development of protective immunity to TB induced by vaccination with BCG.


systematic_name: M41043
exact_source: Suppl Table III
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701477/bin/NIHMS83712-supplement-Supplemetary_t.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with antibody response in peripheral blood mononuclear cell in young adults (18-25) after exposure to HPV-16 L1 VLP , time point 7M. Comment: Spearman Correlation of Gene Expression with Neutralizing Antibody Levels

description_full:
[cell repeats an earlier one in this file: 1766 characters]


systematic_name: M41044
exact_source: Suppl Table III
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701477/bin/NIHMS83712-supplement-Supplemetary_t.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with antibody response in peripheral blood mononuclear cell in young adults (18-25) after exposure to HPV-16 L1 VLP , time point 12M. Comment: Spearman Correlation of Gene Expression with Neutralizing Antibody Levels

description_full:
[cell repeats an earlier one in this file: 1766 characters]


systematic_name: M41045
exact_source: Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/table/T3/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell (5 to 7)d vs 0d in adults (18-40) after exposure to APSV Wetvax , time point 5 to 7D

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M41046
exact_source: Discussion; Fig 4E
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729923/figure/f4/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood poor responders vs responders in seniors (65-83) (poor responders) after exposure to Twinrix , time point 0D. Comment: Networks were inferred for the BioAge module 1 combined to the 15-gene signature and the BioAge module 16 combined to the 15-gene signature, respectively.

description_full:
[cell repeats an earlier one in this file: 1114 characters]


systematic_name: M41047
exact_source: Fig1 & Suppl Fig 3
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-45) after exposure to YF-17D vaccine , time point 3D

description_full:
  A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4-an orchestrator of the integrated stress response-that correlated with and predicted YF-17D CD8(+) T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.

external_details_URL:
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049462/figure/F1/| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049462/bin/NIHMS593578-supplement-01.pdf


systematic_name: M41048
exact_source: Fig1 & Suppl Fig 3
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 7d vs 0d in adults (18-45) after exposure to YF-17D vaccine , time point 7D

description_full:
  A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4-an orchestrator of the integrated stress response-that correlated with and predicted YF-17D CD8(+) T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.

external_details_URL:
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049462/figure/F1/| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049462/bin/NIHMS593578-supplement-01.pdf


systematic_name: M41049
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in neutrophil 7d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 7D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41050
exact_source: Fig 2A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/figure/F2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 7d vs 0d in adults (18-50) after exposure to FluMist , time point 7D. Comment: Molecular signature induced by LAIV vaccination. (a) Interferon (IFN)-related genes differentially expressed after LAIV vaccination

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41051
exact_source: Suppl File 1, Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713456/bin/elife-00299-supp1.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with antibody response in blood in adults (18-40) after exposure to Sanofi Pasteur, SA, Inactivated influenza vaccine , time point 0D

description_full:
[cell repeats an earlier one in this file: 900 characters]


systematic_name: M41052
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/bin/NIHMS29119-supplement-sup_tbl2.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell (4 to 7)d vs 0d in adults (18-40) after exposure to YF-Vax , time point 4 to 7D

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M41053
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 3d and 7d vs 0hr in adults (18-45) (high IgM responders) after exposure to CN54gp140 adjuvanted with GLA-AF , time point 3D, 7D combined (identical signatures) , administered i.m.

description_full:
[cell repeats an earlier one in this file: 2100 characters]

exact_source:
  Results: Early BTM Signatures Induced in Whole Blood Post Vaccination Correlate with Later Serum Antibody Responses


systematic_name: M41054
exact_source: Fig 3C
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068032/figure/fig3/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with a functional network in peripheral blood mononuclear cell in Caucasian male adults (18-40) (high responders) after exposure to Fluarix/Fluvirin , time point 1D. Comment: Top functional network for genes preferentially upregulated in the high responder group

description_full:
  BACKGROUND: Annual vaccination is the primary means for preventing influenza. However, great interindividual variability exists in vaccine responses, the cellular events that take place in vivo after vaccination are poorly understood, and appropriate biomarkers for vaccine responsiveness have not been developed. METHODS: We immunized a cohort of healthy male adults with a licensed trivalent influenza vaccine and performed a timed assessment of global gene expression before and after vaccination. We analyzed the relationship between gene expression patterns and the humoral immune response to vaccination. RESULTS: Marked up regulation of expression of genes involved in interferon signaling, positive IL-6 regulation, and antigen processing and presentation, were detected within 24 hours of immunization. The late vaccine response showed a transcriptional pattern suggestive of increased protein biosynthesis and cellular proliferation. Integrative analyses revealed a 494-gene expression signature--including STAT1, CD74, and E2F2--which strongly correlates with the magnitude of the antibody response. High vaccine responder status correlates with increased early expression of interferon signaling and antigen processing and presentation genes. CONCLUSIONS: The results highlight the role of a systems biology approach in understanding the molecular events that take place in vivo after influenza vaccination and in the development of better predictors of vaccine responsiveness.


systematic_name: M41055
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151076/bin/jiy420_suppl_supplementary_table_1.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in skin of body 3d vs 0hr in adults (70-93) (VZV challenge) after exposure to Zostavax , time point 3D

description_full:
[cell repeats an earlier one in this file: 1437 characters]


systematic_name: M41056
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in natural killer cell 3d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 3D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41057
exact_source: Supplemental Document 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605227/bin/jem.20082292_1.pdf
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 14d vs 0d in unknown after exposure to YF-Vax/Stamaril , time point 14D

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41058
exact_source: s4_mnc_d1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in monocyte 1d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 1D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 1986 characters]


systematic_name: M41059
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986836/table/T2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell (18 to 336)h vs 0h in adults (22-54) after exposure to F. tularensis vaccine LVS , time point 18 to 336H. Comment: Pattern 3, sustained-up. These approx 9 of 42 genes in pattern linked to immune function.

description_full:
[cell repeats an earlier one in this file: 1422 characters]


systematic_name: M41060
exact_source: Fig 5e
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485475/figure/F5/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell high vs low responders in adults (18-64) (medium-high adverse events score) after exposure to Pandemrix , time point 1D. Comment: High AE individuals show day +1 and pre-vaccine differences to asymptomatic study subjects. (e) Genes expressed differentially in low AE vs medium/high AE study subjects on post-vaccine day +1

description_full:
[cell repeats an earlier one in this file: 858 characters]


systematic_name: M41061
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092249/bin/supp_jiu079_jiu079supp_table1.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 7d vs 0d in children (0.5-14y) after exposure to Fluzone , time point 7D. Comment: ~80% of cohort were white, ~50/50 Female:male

description_full:
  BACKGROUND: Live attenuated influenza vaccine (LAIV) and trivalent inactivated influenza vaccine (TIV) are effective for prevention of influenza virus infection in children, but the mechanisms associated with protection are not well defined. METHODS: We analyzed the differences in B-cell responses and transcriptional profiles in children aged 6 months to 14 years immunized with these 2 vaccines. RESULTS: LAIV elicited a significant increase in naive, memory, and transitional B cells on day 30 after vaccination, whereas TIV elicited an increased number of plasmablasts on day 7. Antibody titers against the 3 vaccine strains (H1N1, H3N2, and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Both vaccines induced overexpression of interferon (IFN)-signaling genes but with different kinetics. TIV induced expression of IFN genes on day 1 after vaccination in all age groups, and LAIV induced expression of IFN genes on day 7 after vaccination but only in children < 5 years old. IFN-related genes overexpressed in both vaccinated groups correlated with H3N2 antibody titers. CONCLUSIONS: These results suggest that LAIV and TIV induced significantly different B-cell responses in vaccinated children. Early induction of IFN appears to be important for development of antibody responses.


systematic_name: M41062
exact_source: Suppl Table, see also Fig 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712333/bin/aging-07-1077-s001.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood cohort 1 (re-vaccinated in 6-9 months) vs cohort 2 (re-vaccinated in 12-13 months) in adults (65+) after exposure to 2012-2013 seasonal trivalent inactivated influenza vaccine (TIV) , time point N/A. Comment: Cohort 1 (re-vaccinated in 6-9 months) vs Cohort 2 (re-vaccinated in 12-13 months)

description_full:
  We tested antibody responses to the trivalent inactivated influenza vaccine (TIV) in 34 aged individuals ( > 65 yrs) during the 2012/13 vaccination seasons. Nearly all had been vaccinated the previous year although the time interval between the two vaccine doses differed. One subgroup was re-vaccinated in 2012/13 within 6-9 months of their 2011/12 vaccination, the other received the two doses of vaccine in the typical ~12 month interval. Unexpectedly the sub-cohort with early revaccination exhibited significantly increased response rates and antibody titers to TIV compared to their normally re-vaccinated aged counter parts. Microarray analyses of gene expression in whole blood RNA taken at the day of the 2012/13 re-vaccination revealed statistically significant differences in expression of 754 genes between the individuals with early re-vaccination compared to subjects vaccinated in a normal 12 month interval. These observations suggest that TIV has long-lasting effects on the immune system affecting B cell responses as well as the transcriptome of peripheral blood mononuclear cells and this residual effect may augment vaccination response in patients where the effect of the previous vaccination has not yet diminished.


systematic_name: M41063
exact_source: Supplemental Document 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605227/bin/jem.20082292_1.pdf
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 28d vs 0d in unknown after exposure to YF-Vax/Stamaril , time point 28D

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41064
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 1d vs 0d in adults after exposure to Inactivated influenza vaccine , time point 1D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41065
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834766/bin/Table_2.XLSX
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 6hr vs 0hr in adults (18-45) after exposure to CN54gp140 adjuvanted with GLA-AF , time point 6H , administered i.m.

description_full:
[cell repeats an earlier one in this file: 2100 characters]


systematic_name: M41066
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133148/table/T2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 28d vs 3d in adults (50-74) (in common with both HAI and VNA) after exposure to Fluarix , time point 28D , administered i.m.. Comment: Common Genesets with genes entering regression models for HAI and VNA Responses, withlog2 Day 28 vs Day 3 fold-change in gene expression as the explanatory variables

description_full:
  This study aimed to identify gene expression markers shared between both influenza hemagglutination inhibition (HAI) and virus-neutralization antibody (VNA) responses. We enrolled 158 older subjects who received the 2010-2011 trivalent inactivated influenza vaccine. Influenza-specific HAI and VNA titers and mRNA-sequencing were performed using blood samples obtained at Days 0, 3 and 28 post vaccination. For antibody response at Day 28 versus Day 0, several gene sets were identified as significant in predictive models for HAI (n=7) and VNA (n=35) responses. Five gene sets (comprising the genes MAZ, TTF, GSTM, RABGGTA, SMS, CA, IFNG and DOPEY) were in common for both HAI and VNA. For response at Day 28 versus Day 3, many gene sets were identified in predictive models for HAI (n=13) and VNA (n=41). Ten gene sets (comprising biologically related genes, such as MAN1B1, POLL, CEBPG, FOXP3, IL12A, TLR3, TLR7 and others) were shared between HAI and VNA. These identified gene sets demonstrated a high degree of network interactions and likelihood for functional relationships. Influenza-specific HAI and VNA responses demonstrated a remarkable degree of similarity. Although unique gene set signatures were identified for each humoral outcome, several gene sets were determined to be in common with both HAI and VNA response to influenza vaccine.


systematic_name: M41067
exact_source: Suppl Table 1A, Tab DEGs_TIV
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-2.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-50) after exposure to Fluarix/Fluvirin , time point 3D. Comment: Supplementary Table 1a: All the differentially expressed genes identified in PBMCs of TIV vaccinees.

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41068
exact_source: Fig 6A (PO)
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832504/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in CD4-positive, alpha-beta memory T cell 7d vs 0d in adults (18-45) after exposure to BCG vaccine , time point 7D , administered PO (oral). Comment: top 100 most significantly altered genes comparing Day 0 and Day 7 responses directly ex vivo

description_full:
  Protective efficacy of Bacillus Calmette-Guerin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-gamma production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4<sup>+</sup> memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.


systematic_name: M41069
exact_source: Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133148/table/T1/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 28d vs 0d in adults (50-74) (in common with both HAI and VNA) after exposure to Fluarix , time point 28D , administered i.m.. Comment: Common Genesets with genes entering regression models for HAI and VNA Responses with the log2 Day 28 vs Day 0 fold-change in gene expression as the explanatory variables.

description_full:
  This study aimed to identify gene expression markers shared between both influenza hemagglutination inhibition (HAI) and virus-neutralization antibody (VNA) responses. We enrolled 158 older subjects who received the 2010-2011 trivalent inactivated influenza vaccine. Influenza-specific HAI and VNA titers and mRNA-sequencing were performed using blood samples obtained at Days 0, 3 and 28 post vaccination. For antibody response at Day 28 versus Day 0, several gene sets were identified as significant in predictive models for HAI (n=7) and VNA (n=35) responses. Five gene sets (comprising the genes MAZ, TTF, GSTM, RABGGTA, SMS, CA, IFNG and DOPEY) were in common for both HAI and VNA. For response at Day 28 versus Day 3, many gene sets were identified in predictive models for HAI (n=13) and VNA (n=41). Ten gene sets (comprising biologically related genes, such as MAN1B1, POLL, CEBPG, FOXP3, IL12A, TLR3, TLR7 and others) were shared between HAI and VNA. These identified gene sets demonstrated a high degree of network interactions and likelihood for functional relationships. Influenza-specific HAI and VNA responses demonstrated a remarkable degree of similarity. Although unique gene set signatures were identified for each humoral outcome, several gene sets were determined to be in common with both HAI and VNA response to influenza vaccine.


systematic_name: M41070
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/bin/NIHMS29119-supplement-sup_tbl2.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell (4 to 7)d vs 0d in adults (18-40) after exposure to YF-Vax , time point 4 to 7D

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M41071
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092249/bin/supp_jiu079_jiu079supp_table1.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 30d vs 0d in children (0.5-14y) after exposure to FluMist , time point 30D. Comment: ~80% of cohort were white, ~50/50 Female:male

description_full:
  BACKGROUND: Live attenuated influenza vaccine (LAIV) and trivalent inactivated influenza vaccine (TIV) are effective for prevention of influenza virus infection in children, but the mechanisms associated with protection are not well defined. METHODS: We analyzed the differences in B-cell responses and transcriptional profiles in children aged 6 months to 14 years immunized with these 2 vaccines. RESULTS: LAIV elicited a significant increase in naive, memory, and transitional B cells on day 30 after vaccination, whereas TIV elicited an increased number of plasmablasts on day 7. Antibody titers against the 3 vaccine strains (H1N1, H3N2, and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Both vaccines induced overexpression of interferon (IFN)-signaling genes but with different kinetics. TIV induced expression of IFN genes on day 1 after vaccination in all age groups, and LAIV induced expression of IFN genes on day 7 after vaccination but only in children < 5 years old. IFN-related genes overexpressed in both vaccinated groups correlated with H3N2 antibody titers. CONCLUSIONS: These results suggest that LAIV and TIV induced significantly different B-cell responses in vaccinated children. Early induction of IFN appears to be important for development of antibody responses.


systematic_name: M41072
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood plasma 3d vs 0d in adults (18-55) (high dose) after exposure to rVSV-EBOV , time point 3D

description_full:
  VSV-EBOV is a replication-competent Ebola virus (EBOV) vaccine, which was tested in clinical trials as response to the Ebola virus disease (EVD) outbreak 2013-2016. It is the most advanced EBOV candidate currently in the licensure process. The experimental vaccine was again administered as response to outbreaks in the Democratic Republic of Congo. However, underlying molecular mechanisms that convey protection remain incompletely understood. MicroRNAs (miRNAs) are known key regulators that influence gene expression on a post-transcriptional level. The miRNA-mediated control has emerged as a critical regulatory principle in the immune system, which strongly influences the balance of innate and adaptive immune responses by modulation of signaling pathways critical for differentiation of immune cells. We investigated expression levels of circulating miRNAs (c-miRNAs) in plasma from healthy vaccinees, as they may reflect cellular dynamics following VSV-EBOV immunization and additionally may serve as potential biomarkers for vaccine efficacy. As part of the WHO-led VEBCON consortium, we investigated safety and immunogenicity of VSV-EBOV in a phase I trial. A comprehensive analysis of expression levels on c-miRNAs from plasma samples following VSV-EBOV immunization (day 0, 1, 3 post vaccination) was conducted using RT-qPCR assays. Potential biological relevance was assessed using in silico analyses. Additionally, we correlated dynamics of miRNA expressions with our previously reported data on vaccine-induced antibody and cytokine responses and finally evaluated the prognostic power by generating ROC curves. We identified four promising miRNAs (hsa-miR-146a, hsa-miR-126, hsa-miR-199a, hsa-miR-484), showing a strong association with adaptive immune responses, exhibited favourable prognostic performance and are implicated in immunology-related functions. Our results provide evidence that miRNAs may serve as useful biomarkers for prediction of vaccine-induced immunogenicity. Furthermore, our unique data set provides insight into molecular mechanisms that underlie VSV-EBOV-mediated protective immune responses, which may help to decipher VSV-EBOV immune signature and accelerate strategic vaccine design or personalized approaches.


systematic_name: M41073
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in neutrophil 3d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 3D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41074
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in monocyte 3d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 3D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41075
exact_source: Supplementary Table 2a: LAIV-Monocytes
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-3.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in monocyte 7d vs 0d in young adults (18-50) after exposure to FluMist , time point 7D

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41076
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641062/table/pone-0062149-t002/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in children (13-16) after exposure to M-M-R II , time point 3 to 7Y. Comment: top differentially expressed genes, full set of 1080 avail in Suppl Materials

description_full:
  Immune responses to current rubella vaccines demonstrate significant inter-individual variability. We performed mRNA-Seq profiling on PBMCs from high and low antibody responders to rubella vaccination to delineate transcriptional differences upon viral stimulation. Generalized linear models were used to assess the per gene fold change (FC) for stimulated versus unstimulated samples or the interaction between outcome and stimulation. Model results were evaluated by both FC and p-value. Pathway analysis and self-contained gene set tests were performed for assessment of gene group effects. Of 17,566 detected genes, we identified 1,080 highly significant differentially expressed genes upon viral stimulation (p < 1.00E(-15), FDR < 1.00E(-14)), including various immune function and inflammation-related genes, genes involved in cell signaling, cell regulation and transcription, and genes with unknown function. Analysis by immune outcome and stimulation status identified 27 genes (p <= 0.0006 and FDR <= 0.30) that responded differently to viral stimulation in high vs. low antibody responders, including major histocompatibility complex (MHC) class I genes (HLA-A, HLA-B and B2M with p = 0.0001, p = 0.0005 and p = 0.0002, respectively), and two genes related to innate immunity and inflammation (EMR3 and MEFV with p = 1.46E(-08) and p = 0.0004, respectively). Pathway and gene set analysis also revealed transcriptional differences in antigen presentation and innate/inflammatory gene sets and pathways between high and low responders. Using mRNA-Seq genome-wide transcriptional profiling, we identified antigen presentation and innate/inflammatory genes that may assist in explaining rubella vaccine-induced immune response variations. Such information may provide new scientific insights into vaccine-induced immunity useful in rational vaccine development and immune response monitoring.


systematic_name: M41077
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in T cell 1d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 1D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41078
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in natural killer cell 7d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 7D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41079
exact_source: Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400991/table/T2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell females vs males in adults (50-74) (females) after exposure to Fluarix , time point 0D, 3DY, 28D. Comment: Caucasian adults (50-74); See Suppl Table 6 for full DE gene list, time point 0D, 3DY, 28D combined (identical signatures)

description_full:
  <b>Background:</b> Sex differences in immune responses to influenza vaccine may impact efficacy across populations. <b>Methods:</b> In a cohort of 138 older adults (50-74 years old), we measured influenza A/H1N1 antibody titers, B-cell ELISPOT response, PBMC transcriptomics, and PBMC cell compositions at 0, 3, and 28 days post-immunization with the 2010/11 seasonal inactivated influenza vaccine. <b>Results:</b> We identified higher B-cell ELISPOT responses in females than males. Potential mechanisms for sex effects were identified in four gene clusters related to T, NK, and B cells. Mediation analysis indicated that sex-dependent expression in T and NK cell genes can be partially attributed to higher CD4+ T cell and lower NK cell fractions in females. We identified strong sex effects in 135 B cell genes whose expression correlates with ELISPOT measures, and found that cell subset differences did not explain the effect of sex on these genes' expression. Post-vaccination expression of these genes, however, mediated 41% of the sex effect on ELISPOT responses. <b>Conclusions:</b> These results improve our understanding of sexual dimorphism in immunity and influenza vaccine response.


systematic_name: M41080
exact_source: S2 Table
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987012/bin/pone.0160970.s002.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell vaccinated vs unvaccinated in adolescent/young adults (11-22) after exposure to M-M-R II , time point 7Y

description_full:
  BACKGROUND: There are insufficient system-wide transcriptomic (or other) data that help explain the observed inter-individual variability in antibody titers after measles vaccination in otherwise healthy individuals. METHODS: We performed a transcriptome(mRNA-Seq)-profiling study after in vitro viral stimulation of PBMCs from 30 measles vaccine recipients, selected from a cohort of 764 schoolchildren, based on the highest and lowest antibody titers. We used regression and network biology modeling to define markers associated with neutralizing antibody response. RESULTS: We identified 39 differentially expressed genes that demonstrate significant differences between the high and low antibody responder groups (p-value <= 0.0002, q-value <= 0.092), including the top gene CD93 (p < 1.0E-13, q < 1.0E-09), encoding a receptor required for antigen-driven B-cell differentiation, maintenance of immunoglobulin production and preservation of plasma cells in the bone marrow. Network biology modeling highlighted plasma cell survival (CD93, IL6, CXCL12), chemokine/cytokine activity and cell-cell communication/adhesion/migration as biological processes associated with the observed differential response in the two responder groups. CONCLUSION: We identified genes and pathways that explain in part, and are associated with, neutralizing antibody titers after measles vaccination. This new knowledge could assist in the identification of biomarkers and predictive signatures of protective immunity that may be useful in the design of new vaccine candidates and in clinical studies.


systematic_name: M41081
exact_source: S1 Table
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443534/bin/pntd.0005527.s002.xls
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood 24hr vs 0hr in adults (18-50) (high dose subjects) after exposure to ChAd63-KH , time point 24H , administered Intramuscular injection. Comment: DE gene list for high dose subjects.

description_full:
  BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFN-gamma ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359).


systematic_name: M41082
exact_source: Results: Modulation of gene expression by HIV-LIPO-5
external_details_URL: https://www.ncbi.nlm.nih.gov/pubmed/?term=23759749
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in adults (37-48) after exposure to HIV-LIPO-5 , time point 0W and 14 W. Comment: metallothionein genes, 0W and 14W combined (identical signatures)

description_full:
[cell repeats an earlier one in this file: 1922 characters]


systematic_name: M41083
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092249/bin/supp_jiu079_jiu079supp_table1.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 1d vs 0d in children (0.5-14y) after exposure to FluMist , time point 1D. Comment: ~80% of cohort were white, ~50/50 Female:male

description_full:
[cell repeats an earlier one in this file: 1344 characters]


systematic_name: M41084
exact_source: Suppl Fig 2A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711477/bin/NIHMS871779-supplement-2.tiff
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (25-40/60-79) after exposure to Zostavax , time point 3D

description_full:
  Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4<sup>+</sup> T cells yet limited CD8<sup>+</sup> T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.


systematic_name: M41085
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834766/bin/Table_2.XLSX
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 1d vs 0hr in adults (18-45) after exposure to CN54gp140 adjuvanted with GLA-AF , time point 1D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 2100 characters]


systematic_name: M41086
exact_source: Supplemental Document 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605227/bin/jem.20082292_1.pdf
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 7d vs 0d in unknown after exposure to YF-Vax/Stamaril , time point 7D

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41087
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in T cell 1d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 1D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41088
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in B cell 1d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 1D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41089
exact_source: Suppl Table 1B, Tab DEGs_LAIV
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-2.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-50) after exposure to FluMist , time point 3D. Comment: Supplementary Table 1b: All the differentially expressed genes identified in PBMCs of TIV vaccinees.

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41090
exact_source: Suppl File 1, Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713456/bin/elife-00299-supp1.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with antibody response in blood in adults (18-40) after exposure to Sanofi Pasteur, SA, Inactivated influenza vaccine , time point 14D

description_full:
[cell repeats an earlier one in this file: 900 characters]


systematic_name: M41091
exact_source: Suppl Fig 1D
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520794/bin/NIHMS880612-supplement-Supp_Fig_1.tiff
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with memory B cell response at 28d in peripheral blood mononuclear cell in seniors (50-74) after exposure to Fluarix , time point 28D. Comment: D: Late gene expression individual gene models (predicting peak B cell ELISPOT response) for module 11 (D, MSE=2.062)

description_full:
  BACKGROUND: Studies suggest that the recall-based humoral immune responses to influenza A/H1N1 originates from activated memory B cells. The aim of this study was to identify baseline, early and late blood transcriptional signatures (in peripheral blood mononuclear cells/PBMCs) associated with memory B cell response following influenza vaccination. METHODS: We used pre- and post-vaccination mRNA-Seq transcriptional profiling on samples from 159 subjects (50-74years old) following receipt of seasonal trivalent influenza vaccine containing the A/California/7/2009/H1N1-like virus, and penalized regression modeling to identify associations with influenza A/H1N1-specific memory B cell ELISPOT response after vaccination. RESULTS: Genesets and genes (p-value range 7.92E(-08) to 0.00018, q-value range 0.00019-0.039) demonstrating significant associations (of gene expression levels) with memory B cell response suggest the importance of metabolic (cholesterol and lipid metabolism-related), cell migration/adhesion, MAP kinase, NF-kB cell signaling (chemokine/cytokine signaling) and transcriptional regulation gene signatures in the development of memory B cell response after influenza vaccination. CONCLUSION: Through an unbiased transcriptome-wide profiling approach, our study identified signatures of memory B cell response following influenza vaccination, highlighting the underappreciated role of metabolic changes (among the other immune function-related events) in the regulation of influenza vaccine-induced immune memory.


systematic_name: M41092
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in monocyte 3d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 3D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41093
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 7d vs 0d in adults after exposure to Inactivated influenza vaccine , time point 7D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41094
exact_source: Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551876/table/T3/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 24h vs 0h in adults (18-45) (responders (previously immunized)) after exposure to Live attenuated vaccine TC-83 , time point 24H. Comment: initial exposure 2-10 months before PBMCs drawn. significant genes chosen for membership in canonical pathways

description_full:
  Venezuelan equine encephalitis virus (VEEV) is a positive-strand RNA Alphavirus endemic in Central and South America, and the causative agent of fatal encephalitis in humans. In an effort to better understand the mechanisms of infection, including differences between people who produce a neutralizing antibody response to the vaccine and those who do not, we performed whole genome transcriptional analysis in human PBMCs exposed in vitro to the live-attenuated vaccine strain of VEEV, TC-83. We compared the molecular responses in cells from three groups of individuals: naive; previously vaccinated individuals who developed a neutralizing antibody response to the vaccine (responders); and those who did not develop a neutralizing antibody response to the vaccine (nonresponders). Overall, the changes in gene expression were more intense for the naive group after TC-83 challenge and least potent in the nonresponder group. The main canonical pathways revealed the involvement of interferon and interferon-induced pathways, as well as toll-like receptors TLR- and interleukin (IL)-12-related pathways. HLA class II genotype and suppression of transcript expression for TLR2, TLR4 and TLR8 in the nonresponder group may help explain the lack of vaccine response in this study group. Because TL3 and TLR7 transcripts were elevated in all study groups, these factors may be indicators of the infection and not the immunological state of the individuals. Biomarkers were identified that differentiate between the vaccine responder and the vaccine nonresponder groups. The identified biomarkers were contrasted against transcripts that were unique to the naive population alone upon induction with TC-83. Biomarker analysis allowed for the discernment between the naive (innate) responses; the responder (recall) responses; and the nonresponder (alternative) changes to gene transcription that were caused by infection with TC-83. The study also points to the existence of HLA haplotypes that may discriminate between vaccine low- and high-responder phenotypes.


systematic_name: M41095
exact_source: Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551876/table/T3/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 24h vs 0h in adults (18-45) (naive (not previously immunized)) after exposure to Live attenuated vaccine TC-83 , time point 24H. Comment: significant genes chosen for membership in canonical pathways

description_full:
[cell repeats an earlier one in this file: 2061 characters]


systematic_name: M41096
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092249/bin/supp_jiu079_jiu079supp_table1.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in blood 7d vs 0d in children (0.5-14y) after exposure to FluMist , time point 7D. Comment: ~80% of cohort were white, ~50/50 Female:male

description_full:
[cell repeats an earlier one in this file: 1344 characters]


systematic_name: M41097
exact_source: Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092249/table/JIU079TB3/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with H3N1 HI titer in blood in children (0.5-14y) after exposure to Fluzone , time point 1D. Comment: ~80% of cohort were white, ~50/50 Female:male

description_full:
[cell repeats an earlier one in this file: 1344 characters]


systematic_name: M41098
exact_source: Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092249/table/JIU079TB3/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with H3N2 VN titer in blood in children (0.5-14y) after exposure to FluMist , time point 7D. Comment: ~80% of cohort were white, ~50/50 Female:male

description_full:
[cell repeats an earlier one in this file: 1344 characters]


systematic_name: M41099
exact_source: Suppl Table S1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with memory B cell response at 28d in peripheral blood mononuclear cell in seniors (50-74) after exposure to Fluarix , time point 28D

description_full:
[cell repeats an earlier one in this file: 1537 characters]

external_details_URL:
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520794/bin/NIHMS880612-supplement-Supplemental_Information.docx


systematic_name: M41100
exact_source: Suppl Table S1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with memory B cell response at 28d in peripheral blood mononuclear cell in seniors (50-74) after exposure to Fluarix , time point 3D

description_full:
[cell repeats an earlier one in this file: 1537 characters]

external_details_URL:
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520794/bin/NIHMS880612-supplement-Supplemental_Information.docx


systematic_name: M41101
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 3d vs 0d in adults after exposure to Inactivated influenza vaccine , time point 3D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41102
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092249/bin/supp_jiu079_jiu079supp_table1.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 1d vs 0d in children (0.5-14y) after exposure to Fluzone , time point 1D. Comment: ~80% of cohort were white, ~50/50 Female:male

description_full:
[cell repeats an earlier one in this file: 1344 characters]


systematic_name: M41103
exact_source: Suppl Table 5
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-6.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with HAI response at 28d in peripheral blood mononuclear cell in adults (18-50) after exposure to Fluarix/Fluvirin , time point 3D. Comment: Supplementary Table 5: All genes whose expression (d3/d0 or d7/d0) correlates to the fold increase in HAI titers (d28/d0).

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41104
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092249/bin/supp_jiu079_jiu079supp_table1.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 30d vs 0d in children (0.5-14y) after exposure to Fluzone , time point 30D. Comment: ~80% of cohort were white, ~50/50 Female:male

description_full:
[cell repeats an earlier one in this file: 1344 characters]


systematic_name: M41105
exact_source: Supplementary Table 2a: TIV-pDC
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-3.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in plasmacytoid dendritic cell 7d vs 0d in young adults (18-50) after exposure to Fluarix/Fluvirin , time point 7D

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41106
exact_source: S7 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s007.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in neutrophil 1d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 1D. Comment: Down-regulated DE RNA transcripts (down >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41107
exact_source: Fig 4B-D
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763735/figure/fig04/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell 1d postboost vs 0d pre-imm in children (14-27m) (MF59-adjuvanted) after exposure to Fluad , time point 1D. Comment: (B) Genes in BTM M7.0; (D) Genes in BTM M53

description_full:
[cell repeats an earlier one in this file: 1291 characters]


systematic_name: M41108
exact_source: s4_nkc_d3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in natural killer cell 3d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 3D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 1986 characters]


systematic_name: M41109
exact_source: s4_neu_d3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242433/bin/pone.0167488.s005.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in neutrophil 3d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 3D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 1986 characters]


systematic_name: M41110
exact_source: Suppl File 1, Table 3
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713456/bin/elife-00299-supp1.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with antibody response in blood in adults (18-40) after exposure to Sanofi Pasteur, SA, Inactivated influenza vaccine , time point 1D

description_full:
[cell repeats an earlier one in this file: 900 characters]


systematic_name: M41111
exact_source: Fig 2A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/figure/F2/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 3d vs 0d in adults (18-50) after exposure to FluMist , time point 3D. Comment: Molecular signature induced by LAIV vaccination. (a) Interferon (IFN)-related genes differentially expressed after LAIV vaccination

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41112
exact_source: Supplementary Table 2a: TIV-Bcells
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-3.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in B cell 7d vs 0d in young adults (18-50) after exposure to Fluarix/Fluvirin , time point 7D

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41113
exact_source: Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987012/table/pone.0160970.t001/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell vaccinated vs unvaccinated in adolescent/young adults (11-22) (low antibody responders to treatment) after exposure to M-M-R II , time point 7Y

description_full:
[cell repeats an earlier one in this file: 1584 characters]


systematic_name: M41114
exact_source: S6 Dataset
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338067/bin/pone.0118528.s006.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in T cell 3d vs 0d in adults after exposure to 2011-2012 trivalent inactivated vaccine (A/California/7/09 (H1N1), A/Perth /16/2009 (H3N2), B/Brisbane/60/2008) , time point 3D. Comment: Up-regulated DE RNA transcripts (up >= 1.5x) shared between both TIV-vaccinated donors

description_full:
[cell repeats an earlier one in this file: 1424 characters]


systematic_name: M41115
exact_source: Suppl Table S1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with memory B cell response at 28d in peripheral blood mononuclear cell in seniors (50-74) after exposure to Fluarix , time point 0D

description_full:
[cell repeats an earlier one in this file: 1537 characters]

external_details_URL:
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520794/bin/NIHMS880612-supplement-Supplemental_Information.docx


systematic_name: M41116
exact_source: Fig 6A (ID)
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832504/figure/F6/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in CD4-positive, alpha-beta memory T cell 7d vs 0d in adults (18-45) after exposure to BCG vaccine , time point 7D , administered ID (intradermal). Comment: top 100 most significantly altered genes comparing Day 0 and Day 7 responses directly ex vivo

description_full:
[cell repeats an earlier one in this file: 1343 characters]


systematic_name: M41117
exact_source: Suppl Table 1
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092249/bin/supp_jiu079_jiu079supp_table1.doc
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 7d vs 0d in children (0.5-14y) after exposure to FluMist , time point 7D. Comment: ~80% of cohort were white, ~50/50 Female:male

description_full:
[cell repeats an earlier one in this file: 1344 characters]


systematic_name: M41118
exact_source: Suppl Table S1
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes negatively correlated with memory B cell response at 28d in peripheral blood mononuclear cell in seniors (50-74) after exposure to Fluarix , time point 3D

description_full:
[cell repeats an earlier one in this file: 1537 characters]

external_details_URL:
[cell repeats an earlier one in this file: 109 characters]


systematic_name: M41119
exact_source: Table 4
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/table/T4/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell in adults (18-40) after exposure to YF-Vax , time point anyD

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M41120
exact_source: Fig 5A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338562/figure/fig05/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes positively correlated with protection in peripheral blood mononuclear cell in unknown after exposure to P. falciparum RTS,S/AS01 , time point 56D

description_full:
  RTS,S is an advanced malaria vaccine candidate and confers significant protection against <i>Plasmodium falciparum</i> infection in humans. Little is known about the molecular mechanisms driving vaccine immunity. Here, we applied a systems biology approach to study immune responses in subjects receiving three consecutive immunizations with RTS,S (RRR), or in those receiving two immunizations of RTS,S/AS01 following a primary immunization with adenovirus 35 (Ad35) (ARR) vector expressing circumsporozoite protein. Subsequent controlled human malaria challenge (CHMI) of the vaccinees with <i>Plasmodium</i>-infected mosquitoes, 3 wk after the final immunization, resulted in ~50% protection in both groups of vaccinees. Circumsporozoite protein (CSP)-specific antibody titers, prechallenge, were associated with protection in the RRR group. In contrast, ARR-induced lower antibody responses, and protection was associated with polyfunctional CD4<sup>+</sup> T-cell responses 2 wk after priming with Ad35. Molecular signatures of B and plasma cells detected in PBMCs were highly correlated with antibody titers prechallenge and protection in the RRR cohort. In contrast, early signatures of innate immunity and dendritic cell activation were highly associated with protection in the ARR cohort. For both vaccine regimens, natural killer (NK) cell signatures negatively correlated with and predicted protection. These results suggest that protective immunity against <i>P. falciparum</i> can be achieved via multiple mechanisms and highlight the utility of systems approaches in defining molecular correlates of protection to vaccination.


systematic_name: M41121
exact_source: Suppl Table 2
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834766/bin/Table_2.XLSX
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in blood 7d vs 0hr in adults (18-45) after exposure to CN54gp140 adjuvanted with GLA-AF , time point 7D , administered i.m.

description_full:
[cell repeats an earlier one in this file: 2100 characters]


systematic_name: M41122
exact_source: Supplementary Table 2a: LAIV-pDC
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140559/bin/NIHMS301940-supplement-3.xlsx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in plasmacytoid dendritic cell 7d vs 0d in young adults (18-50) after exposure to FluMist , time point 7D

description_full:
[cell repeats an earlier one in this file: 949 characters]


systematic_name: M41123
exact_source: S2 Table
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072604/bin/ppat.1005892.s002.docx
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 1d vs 0d in seniors (50-75) after exposure to Zostavax , time point 1D. Comment: S2 Table has Illumina probe IDs

description_full:
[cell repeats an earlier one in this file: 1196 characters]


systematic_name: M41124
exact_source: Suppl Fig 2A
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711477/bin/NIHMS871779-supplement-2.tiff
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell 1d vs 0d in adults (25-40/60-79) after exposure to Zostavax , time point 1D

description_full:
  Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4<sup>+</sup> T cells yet limited CD8<sup>+</sup> T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.


systematic_name: M41125
exact_source: Figure 4
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800877/figure/F4/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes down-regulated in peripheral blood mononuclear cell high responders vs low responders in younger adults (21-35) (high responders) after exposure to trivalent influenza vaccine (TIV) , time point 0D. Comment: data from six different cohorts, trivalent vaccine year not specified

description_full:
  Annual influenza vaccinations are currently recommended for all individuals 6 months and older. Antibodies induced by vaccination are an important mechanism of protection against infection. Despite the overall public health success of influenza vaccination, many individuals fail to induce a substantial antibody response. Systems-level immune profiling studies have discerned associations between transcriptional and cell subset signatures with the success of antibody responses. However, existing signatures have relied on small cohorts and have not been validated in large independent studies. We leveraged multiple influenza vaccination cohorts spanning distinct geographical locations and seasons from the Human Immunology Project Consortium (HIPC) and the Center for Human Immunology (CHI) to identify baseline (i.e., before vaccination) predictive transcriptional signatures of influenza vaccination responses. Our multicohort analysis of HIPC data identified nine genes (<i>RAB24</i>, <i>GRB2</i>, <i>DPP3</i>, <i>ACTB</i>, <i>MVP</i>, <i>DPP7</i>, <i>ARPC4</i>, <i>PLEKHB2</i>, and <i>ARRB1</i>) and three gene modules that were significantly associated with the magnitude of the antibody response, and these associations were validated in the independent CHI cohort. These signatures were specific to young individuals, suggesting that distinct mechanisms underlie the lower vaccine response in older individuals. We found an inverse correlation between the effect size of signatures in young and older individuals. Although the presence of an inflammatory gene signature, for example, was associated with better antibody responses in young individuals, it was associated with worse responses in older individuals. These results point to the prospect of predicting antibody responses before vaccination and provide insights into the biological mechanisms underlying successful vaccination responses.


systematic_name: M41126
exact_source: Table 4
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211276/table/T4/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell in adults (18-40) after exposure to YF-Vax , time point anyD

description_full:
[cell repeats an earlier one in this file: 1030 characters]


systematic_name: M41127
exact_source: Figure 4
external_details_URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800877/figure/F4/
source_species_code: HS
contributor: HIPC SIGNATURES
contrib_organization: NIAID/HIPC SIGNATURES
description_brief:
  Genes up-regulated in peripheral blood mononuclear cell high responders vs low responders in younger adults (21-35) (high responders) after exposure to trivalent influenza vaccine (TIV) , time point 0D. Comment: data from six different cohorts, trivalent vaccine year not specified

description_full:
  Annual influenza vaccinations are currently recommended for all individuals 6 months and older. Antibodies induced by vaccination are an important mechanism of protection against infection. Despite the overall public health success of influenza vaccination, many individuals fail to induce a substantial antibody response. Systems-level immune profiling studies have discerned associations between transcriptional and cell subset signatures with the success of antibody responses. However, existing signatures have relied on small cohorts and have not been validated in large independent studies. We leveraged multiple influenza vaccination cohorts spanning distinct geographical locations and seasons from the Human Immunology Project Consortium (HIPC) and the Center for Human Immunology (CHI) to identify baseline (i.e., before vaccination) predictive transcriptional signatures of influenza vaccination responses. Our multicohort analysis of HIPC data identified nine genes (<i>RAB24</i>, <i>GRB2</i>, <i>DPP3</i>, <i>ACTB</i>, <i>MVP</i>, <i>DPP7</i>, <i>ARPC4</i>, <i>PLEKHB2</i>, and <i>ARRB1</i>) and three gene modules that were significantly associated with the magnitude of the antibody response, and these associations were validated in the independent CHI cohort. These signatures were specific to young individuals, suggesting that distinct mechanisms underlie the lower vaccine response in older individuals. We found an inverse correlation between the effect size of signatures in young and older individuals. Although the presence of an inflammatory gene signature, for example, was associated with better antibody responses in young individuals, it was associated with worse responses in older individuals. These results point to the prospect of predicting antibody responses before vaccination and provide insights into the biological mechanisms underlying successful vaccination responses.


