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

 

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dc.contributor.author Gideon, Hannah Priyadarshini en_ZA
dc.contributor.author Wilkinson, Katalin Andrea en_ZA
dc.contributor.author Rustad, Tige R en_ZA
dc.contributor.author Oni, Tolu en_ZA
dc.contributor.author Guio, Heinner en_ZA
dc.contributor.author Kozak, Robert Andrew en_ZA
dc.contributor.author Sherman, David R en_ZA
dc.contributor.author Meintjes, Graeme en_ZA
dc.contributor.author Behr, Marcel A en_ZA
dc.contributor.author Vordermeier, Hans Martin en_ZA
dc.date.accessioned 2016-01-02T05:05:43Z
dc.date.available 2016-01-02T05:05:43Z
dc.date.issued 2010 en_ZA
dc.identifier.citation Gideon, 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.1001237 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16155
dc.identifier.uri http://dx.doi.org/10.1371/journal.ppat.1001237
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plospathogens en_ZA
dc.subject.other Mycobacterium tuberculosis en_ZA
dc.subject.other Cytokines en_ZA
dc.subject.other Tuberculosis en_ZA
dc.subject.other HIV infections en_ZA
dc.subject.other T cells en_ZA
dc.subject.other Hypoxia en_ZA
dc.subject.other Enzyme-linked immunoassays en_ZA
dc.subject.other Immune response en_ZA
dc.title Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2010 Gideon et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
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This 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. Except where otherwise noted, this item's license is described as This 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.