Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines

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dc.contributor.authorGideon, Hannah Priyadarshinien_ZA
dc.contributor.authorWilkinson, Katalin Andreaen_ZA
dc.contributor.authorRustad, Tige Ren_ZA
dc.contributor.authorOni, Toluen_ZA
dc.contributor.authorGuio, Heinneren_ZA
dc.contributor.authorKozak, Robert Andrewen_ZA
dc.contributor.authorSherman, David Ren_ZA
dc.contributor.authorMeintjes, Graemeen_ZA
dc.contributor.authorBehr, Marcel Aen_ZA
dc.contributor.authorVordermeier, Hans Martinen_ZA
dc.date.accessioned2016-01-02T05:05:43Z
dc.date.available2016-01-02T05:05:43Z
dc.date.issued2010en_ZA
dc.description.abstractAuthor Summary Mycobacterium tuberculosis (the cause of tuberculosis) can persist for many years in humans without causing disease but has the potential to reactivate. One of the conditions the bacterium must survive in these circumstances is hypoxia. In order to do so, the bacterium uses a characteristic set of genes that help alter its metabolism. It follows that the products of such genes may encode protein antigens that can be recognized by the immune response. We therefore analyzed gene response patterns of tuberculosis subject to prolonged hypoxia as a guide to the discovery of new antigens that might be useful as vaccines or diagnostic agents. Amongst the genes most strongly increased by low oxygen levels, one was identified (known as Rv1986) that is missing from most strains of the tuberculosis vaccine Mycobacterium bovis BCG. When we analyzed human immune responses to this protein in tuberculosis infected people our experiments showed it was particularly well recognized by cells that produce a chemical messenger (cytokine) called interleukin-2. Interleukin-2 is important for long-term immunological memory. The BCG vaccine is only partially effective and our experiments therefore suggest one of the reasons could be that an important immunological target is missing from many strains. Further evaluation of BCG strains in which Rv1986 is present or absent is therefore warranted in the hope that this might improve the efficacy of existing or new tuberculosis vaccines.en_ZA
dc.identifier.apacitationGideon, H. P., Wilkinson, K. A., Rustad, T. R., Oni, T., Guio, H., Kozak, R. A., ... Vordermeier, H. M. (2010). Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines. <i>PLoS One</i>, http://hdl.handle.net/11427/16155en_ZA
dc.identifier.chicagocitationGideon, Hannah Priyadarshini, Katalin Andrea Wilkinson, Tige R Rustad, Tolu Oni, Heinner Guio, Robert Andrew Kozak, David R Sherman, Graeme Meintjes, Marcel A Behr, and Hans Martin Vordermeier "Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines." <i>PLoS One</i> (2010) http://hdl.handle.net/11427/16155en_ZA
dc.identifier.citationGideon, H. P., Wilkinson, K. A., Rustad, T. R., Oni, T., Guio, H., Kozak, R. A., ... & Young, D. B. (2010). Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines. PLoS Pathog, 6(12), e1001237. doi:10.1371/journal.ppat.1001237en_ZA
dc.identifier.ris TY - Journal Article AU - Gideon, Hannah Priyadarshini AU - Wilkinson, Katalin Andrea AU - Rustad, Tige R AU - Oni, Tolu AU - Guio, Heinner AU - Kozak, Robert Andrew AU - Sherman, David R AU - Meintjes, Graeme AU - Behr, Marcel A AU - Vordermeier, Hans Martin AB - Author Summary Mycobacterium tuberculosis (the cause of tuberculosis) can persist for many years in humans without causing disease but has the potential to reactivate. One of the conditions the bacterium must survive in these circumstances is hypoxia. In order to do so, the bacterium uses a characteristic set of genes that help alter its metabolism. It follows that the products of such genes may encode protein antigens that can be recognized by the immune response. We therefore analyzed gene response patterns of tuberculosis subject to prolonged hypoxia as a guide to the discovery of new antigens that might be useful as vaccines or diagnostic agents. Amongst the genes most strongly increased by low oxygen levels, one was identified (known as Rv1986) that is missing from most strains of the tuberculosis vaccine Mycobacterium bovis BCG. When we analyzed human immune responses to this protein in tuberculosis infected people our experiments showed it was particularly well recognized by cells that produce a chemical messenger (cytokine) called interleukin-2. Interleukin-2 is important for long-term immunological memory. The BCG vaccine is only partially effective and our experiments therefore suggest one of the reasons could be that an important immunological target is missing from many strains. Further evaluation of BCG strains in which Rv1986 is present or absent is therefore warranted in the hope that this might improve the efficacy of existing or new tuberculosis vaccines. DA - 2010 DB - OpenUCT DO - 10.1371/journal.ppat.1001237 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines TI - Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines UR - http://hdl.handle.net/11427/16155 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16155
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.1001237
dc.identifier.vancouvercitationGideon HP, Wilkinson KA, Rustad TR, Oni T, Guio H, Kozak RA, et al. Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines. PLoS One. 2010; http://hdl.handle.net/11427/16155.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2010 Gideon et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherHIV infectionsen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherHypoxiaen_ZA
dc.subject.otherEnzyme-linked immunoassaysen_ZA
dc.subject.otherImmune responseen_ZA
dc.titleHypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccinesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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