Analysis of host responses to secreted, latent and reactivation Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa

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dc.contributor.authorSutherland, Jayne S.en_ZA
dc.contributor.authorLalor, Maeve K.en_ZA
dc.contributor.authorBlack, Gillian F.en_ZA
dc.contributor.authorAmbrose, Lyn R.en_ZA
dc.contributor.authorLoxton, Andre G.en_ZA
dc.contributor.authorChegou, Novel N.en_ZA
dc.contributor.authorKassa, Destaen_ZA
dc.contributor.authorMihret, Adaneen_ZA
dc.contributor.authorHowe, Rawleighen_ZA
dc.contributor.authorMayanja-Kizza, Harrieten_ZA
dc.contributor.authorGomez, Marie P.en_ZA
dc.contributor.authorDonkor, Simonen_ZA
dc.contributor.authorFranken, Keesen_ZA
dc.contributor.authorBoom, W. Henryen_ZA
dc.contributor.authorThiel, Bonnie A.en_ZA
dc.contributor.authorCrampin, Amelia C.en_ZA
dc.contributor.authorHanekom, Willemen_ZA
dc.contributor.authorKlein, Michel R.en_ZA
dc.contributor.authorParida, Shreemanta K.en_ZA
dc.contributor.authorOta, Martinen_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorOttenhoff, Tom H. M.en_ZA
dc.contributor.authorDockrell, Hazel M.en_ZA
dc.contributor.authorKaufmann, Stefan H. E.en_ZA
dc.date.accessioned2014-07-07T12:18:39Z
dc.date.available2014-07-07T12:18:39Z
dc.date.issued2013-09-10
dc.descriptionCITATION: Sutherland, J. S. et al. 2013. Analysis of host responses to secreted, latent and reactivation Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa. PLoS ONE, 8(9): e74080, doi:10.1371/journal.pone.0074080.
dc.descriptionThe original publication is available at http://journals.plos.org/plosone
dc.description.abstractBackground: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. Methods: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. Results: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST- and TST+ contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST+ contacts (LTBI) compared to TB and TST- contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. Conclusions: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials.
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074080
dc.description.versionPublisher's version
dc.format.extent14 pages
dc.identifier.citationSutherland, J. S. et al. 2013. Analysis of host responses to secreted, latent and reactivation Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa. PLoS ONE, 8(9): e74080, doi:10.1371/journal.pone.0074080.
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0074080
dc.identifier.urihttp://hdl.handle.net/10019.1/93399
dc.language.isoen
dc.publisherPublic Library of Science
dc.rights.holderAuthors retain copyright
dc.subjectTuberculosisen_ZA
dc.subjectTuberculosis -- Africa, Sub-Saharanen_ZA
dc.subjectHIV infections -- Africa, Sub-Saharanen_ZA
dc.titleAnalysis of host responses to secreted, latent and reactivation Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africaen_ZA
dc.typeArticle
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