Human Gene Set: MATSUMIYA_PBMC_MODIFIED_VACCINIA_ANKARA
      _VACCINE_AGE_18_55YO_HIGH_RESPONDERS_VS
      _LOW_RESPONDERS_0DY_UP

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Standard name MATSUMIYA_PBMC_MODIFIED_VACCINIA_ANKARA_VACCINE_AGE_18_55YO_HIGH_RESPONDERS_VS_LOW_RESPONDERS_0DY_UP
Systematic name M40953
Brief description 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
Full description or abstract 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.
Collection C7: Immunologic Signature
      VAX: HIPC Vaccine Response
Source publication Pubmed 23844129   Authors: Matsumiya M,Stylianou E,Griffiths K,Lang Z,Meyer J,Harris SA,Rowland R,Minassian AM,Pathan AA,Fletcher H,McShane H
Exact source Fig 3A
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External links https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700883/figure/pone-0067922-g003/
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Organism Homo sapiens
Contributed by HIPC SIGNATURES (NIAID/HIPC SIGNATURES)
Source platform HUMAN_GENE_SYMBOL
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Version history 7.3: First Introduced.

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