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Gene expression analysis of peripheral blood mononuclear cells prior to and following vaccination of human volunteers with the novel TB vaccine candidate MVA85A

ABSTRACT: A greater understanding of the relationships between a vaccine, the immune response it induces, and protection from disease would greatly facilitate vaccine development. Modified Vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis (TB) vaccine designed to enhance responses induced by Bacille Calmette-Guerin (BCG). Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A and peaks one week post-vaccination, however, the variability in response between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression following vaccination with MVA85A and understand how these are related to long-term immunogenicity. 24 volunteers were vaccinated with 10^8 pfu MVA85A. 12 volunteers were vaccinated intramuscularly and 12 intradermally. Volunteers were healthy and did not have HIV, HCV, HBV or latent or active tuberculosis. Blood for this study was taken on the day of vaccination, immediately prior to the vaccine being given (day 0), and 2 and 7 days post-vaccination.

ORGANISM(S): Homo sapiens

PROVIDER: GSE40719 | GEO | 2012/09/28

SECONDARY ACCESSION(S): PRJNA174748

REPOSITORIES: GEO

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Project description: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-γ 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-γ 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 registration: ClinicalTrials.gov number NCT00953927 PBMC collected pre or 28 days post vaccinated, stimulated with either Ag85A peptides (20 samples) or media alone (60).

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Gene expression analysis of peripheral blood mononuclear cells prior to and following vaccination of human volunteers with the novel TB vaccine candidate MVA85A

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