Abstract
Tuberculosis is out of control in developing countries, where it is killing millions of people every year. In these areas, the present vaccine — Mycobacterium bovis bacillus Calmette–Guérin (BCG) — is failing. Progressive tuberculosis occurs because the potentially protective T helper 1 (TH1)-cell response is converted to an immunopathological response that fails to eliminate the bacteria. Here, we discuss the data indicating that the problem in developing countries is not a lack of adequate TH1-cell responses but, instead, an exaggerated tendency to switch to immunopathological responses. We propose that a successful vaccine needs to block this immunopathology, because it is not the quantity of TH1-cell activity that matters but, rather, its context.
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Acknowledgements
We are grateful to the European Union International Cooperation with Developing Countries (INCO-DEV) Fifth Framework Programme for supporting this work. K.D. was supported by a grant from the British Lung Foundation.
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Graham Rook is a shareholder in SR Pharma plc (United Kingdom), which owns intellectual property relating to Mycobacterium vaccae.
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Rook, G., Dheda, K. & Zumla, A. Immune responses to tuberculosis in developing countries: implications for new vaccines. Nat Rev Immunol 5, 661–667 (2005). https://doi.org/10.1038/nri1666
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DOI: https://doi.org/10.1038/nri1666
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