Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response

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dc.contributor.authorMatsumiya, Magalien_ZA
dc.contributor.authorHarris, Stephanie A.en_ZA
dc.contributor.authorSatti, Imanen_ZA
dc.contributor.authorStockdale, Lisaen_ZA
dc.contributor.authorTanner, Rachelen_ZA
dc.contributor.authorO’Shea, Matthew K.en_ZA
dc.contributor.authorTameris, Michelleen_ZA
dc.contributor.authorMahomed, Hassanen_ZA
dc.contributor.authorHatherill, Marken_ZA
dc.contributor.authorScriba, Thomas J.en_ZA
dc.contributor.authorHanekom, Willem A.en_ZA
dc.contributor.authorMcShane, Helenen_ZA
dc.contributor.authorFletcher, Helen A.en_ZA
dc.date.accessioned2016-07-06T13:46:07Z
dc.date.available2016-07-06T13:46:07Z
dc.date.issued2014-06
dc.descriptionCITATION: Matsumiya, M. et al. 2014. Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response. BMC Infectious Diseases, 14:314, doi:10.1186/1471-2334-14-314.en_ZA
dc.descriptionThe original publication is available at http://bmcinfectdis.biomedcentral.comen_ZA
dc.description.abstractBackground: 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.en_ZA
dc.description.urihttp://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-14-314
dc.description.versionPublisher's versionen_ZA
dc.format.extent14 pages : illustrations
dc.identifier.citationMatsumiya, M. et al. 2014. Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response. BMC Infectious Diseases, 14:314, doi:10.1186/1471-2334-14-314.en_ZA
dc.identifier.issn1471-2334 (online)
dc.identifier.otherdoi:10.1186/1471-2334-14-314
dc.identifier.urihttp://hdl.handle.net/10019.1/99098
dc.language.isoen_ZAen_ZA
dc.publisherBioMed Centralen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTuberculosis -- Vaccination -- South Africaen_ZA
dc.subjectImmunization of children -- South Africaen_ZA
dc.subjectNatural immunity -- South Africaen_ZA
dc.subjectImmune responseen_ZA
dc.subjectMVA85Aen_ZA
dc.titleInflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell responseen_ZA
dc.typeArticleen_ZA
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