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

dc.contributor.authorMatsumiya, Magali
dc.contributor.authorHarris, Stephanie A
dc.contributor.authorSatti, Iman
dc.contributor.authorStockdale, Lisa
dc.contributor.authorTanner, Rachel
dc.contributor.authorO’Shea, Matthew K
dc.contributor.authorTameris, Michelle
dc.contributor.authorMahomed, Hassan
dc.contributor.authorHatherill, Mark
dc.contributor.authorScriba, Thomas J
dc.contributor.authorHanekom, Willem A
dc.contributor.authorMcShane, Helen
dc.contributor.authorFletcher, Helen A
dc.date.accessioned2015-07-30T03:51:07Z
dc.date.available2015-07-30T03:51:07Z
dc.date.issued2014-06-09
dc.date.updated2015-01-15T17:57:28Z
dc.description.abstractAbstract 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
dc.identifier.apacitationMatsumiya, M., Harris, S. A., Satti, I., Stockdale, L., Tanner, R., , ... Fletcher, H. A. (2014). Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response. <i>BMC Infectious Diseases</i>, http://hdl.handle.net/11427/13578en_ZA
dc.identifier.chicagocitationMatsumiya, Magali, Stephanie A Harris, Iman Satti, Lisa Stockdale, Rachel Tanner, , Michelle Tameris, et al "Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response." <i>BMC Infectious Diseases</i> (2014) http://hdl.handle.net/11427/13578en_ZA
dc.identifier.citationMatsumiya, M., Harris, S. A., Satti, I., Stockdale, L., Tanner, R., Matthew, K. O., ... & Fletcher, H. A. (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(1), 314.
dc.identifier.ris TY - Journal Article AU - Matsumiya, Magali AU - Harris, Stephanie A AU - Satti, Iman AU - Stockdale, Lisa AU - Tanner, Rachel AU - O’Shea, Matthew K AU - Tameris, Michelle AU - Mahomed, Hassan AU - Hatherill, Mark AU - Scriba, Thomas J AU - Hanekom, Willem A AU - McShane, Helen AU - Fletcher, Helen A AB - 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-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 DA - 2014-06-09 DB - OpenUCT DO - 10.1186/1471-2334-14-314 DP - University of Cape Town J1 - BMC Infectious Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response TI - Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response UR - http://hdl.handle.net/11427/13578 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/13578
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2334-14-314
dc.identifier.vancouvercitationMatsumiya M, Harris SA, Satti I, Stockdale L, Tanner R, , et al. 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. 2014; http://hdl.handle.net/11427/13578.en_ZA
dc.language.rfc3066en
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License*
dc.rights.holderMatsumiya et al.; licensee BioMed Central Ltd.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0*
dc.sourceBMC Infectious Diseasesen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcinfectdis/
dc.subject.otherTuberculosisen_ZA
dc.subject.otherVaccineen_ZA
dc.subject.otherInnate immunityen_ZA
dc.subject.otherTranscriptomicsen_ZA
dc.subject.otherMVA85Aen_ZA
dc.titleInflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response
dc.typeJournal Articleen_ZA
uct.type.filetype
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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