Systematic name M40990
Brief description 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
Full description or abstract 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: number NCT00953927.
Collection C7: Immunologic Signature
      VAX: HIPC Vaccine Response
Source publication Pubmed 24912498   Authors: Matsumiya M,Harris SA,Satti I,Stockdale L,Tanner R,O'Shea MK,Tameris M,Mahomed H,Hatherill M,Scriba TJ,Hanekom WA,McShane H,Fletcher HA
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Organism Homo sapiens
Source platform HUMAN_GENE_SYMBOL
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