GSEA and MSigDB Need Your Support

We are preparing a grant proposal to NCI's Information Technology for Cancer Research program for the continued funding of GSEA and MSigDB. Click here to learn how you can help. (show)

Systematic name M41034
Brief description 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
Full description or abstract 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-naïve 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, ?10(6)- < 10(7)CFU=high dose) or non-recombinant Tice BCG (1-8?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. 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-γ 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.
Collection C7: Immunologic Signature
      VAX: HIPC Vaccine Response
Source publication Pubmed 27322481   Authors: Hoft DF,Blazevic A,Selimovic A,Turan A,Tennant J,Abate G,Fulkerson J,Zak DE,Walker R,McClain B,Sadoff J,Scott J,Shepherd B,Ishmukhamedov J,Hokey DA,Dheenadhayalan V,Shankar S,Amon L,Navarro G,Podyminogin R,Aderem A,Barker L,Brennan M,Wallis RS,Gershon AA,Gershon MD,Steinberg S
Exact source Fig 7A
Related gene sets (show 210 gene sets from the same authors)
External links
Filtered by similarity ?
Organism Homo sapiens
Source platform HUMAN_GENE_SYMBOL
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 40 genes
Gene families ? Categorize these 40 genes by gene family
Show members (show 40 members mapped to 40 genes)
Version history 7.3: First Introduced.

See MSigDB license terms here. Please note that certain gene sets have special access terms.