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Immune responses to tuberculosis in developing countries: implications for new vaccines

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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Figure 1: Phases of infection Mycobacterium tuberculosis.
Figure 2: Events that might lead to failure of BCG in developing countries.

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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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Correspondence to Graham A. W. Rook.

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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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DATABASES

Entrez Gene

FOXP3

IL-2

IL-4

IL-5

IL-10

IL-18

sigH

whiB3

OMIM

asthma

malaria

rheumatoid arthritis

tuberculosis

FURTHER INFORMATION

Aeras Global TB Vaccine Foundation

AnHui Longcom Biologic Pharmacy Company Limited

DARDAR Health Study

UCL Centre for Infectious Diseases and International Health

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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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