MRC National Institute for Medical Research, London
Science for Health
Hypoxia provides a clue to BCG vaccine effectiveness
11 January 2011
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.
Robert Wilkinson (pictured) and Douglas Young, from NIMR's Division of Mycobacterial Research worked with collaborators at the Seattle Biomedical Research Institute to analyse 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 they analysed human immune responses to this protein in tuberculosis-infected people they found that it was particularly well-recognised by cells that produce a chemical messenger (cytokine) called interleukin-2, which is important for long-term immunological memory.
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 this might improve the efficacy of existing or new tuberculosis vaccines.
Robert Wilkinson
Original article
Hannah Priyadarshini Gideon, Katalin Andrea Wilkinson, Tige R. Rustad, Tolu Oni, Heinner Guio, Robert Andrew Kozak, David R. Sherman, Graeme Meintjes, Marcel A. Behr, Hans Martin Vordermeier, Douglas Brownlee Young, Robert John Wilkinson (2010).
Hypoxia Induces an Immunodominant Target of Tuberculosis Specific T Cells Absent from Common BCG Vaccines
PLoS Pathogens, 6(12): e1001237 Article fulltext
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