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Therapy of tuberculosis in mice by DNA vaccination

Nature volume 400, pages 269–271 (1999)Cite this article

Abstract

Mycobacterium tuberculosis continues to kill about 3 million people every year1, more than any other single infectious agent. This is attributed primarily to an inadequate immune response towards infecting bacteria, which suffer growth inhibition rather than death and subsequently multiply catastrophically. Although the bacillus Calmette–Guérin (BCG) vaccine is widely used, it has major limitations as a preventative measure2. In addition, effective treatment requires that patients take large doses of antibacterial drug combinations for at least 6 months after diagnosis3, which is difficult to achieve in many parts of the world and is further restricted by the emergence of multidrug-resistant strains of M. tuberculosis. In these circumstances, immunotherapy to boost the efficiency of the immune system in infected patients could be a valuable adjunct to antibacterial chemotherapy4. Here we show in mice that DNA vaccines, initially designed to prevent infection, can also have a pronounced therapeutic action. In heavily infected mice, DNA vaccinations can switch the immune response from one that is relatively inefficient and gives bacterial stasis to one that kills bacteria. Application of such immunotherapy in conjunction with conventional chemotherapeutic antibacterial drugs might result in faster or more certain cure of the disease in humans.

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Figure 1: Therapeutic effects of DNA vaccination against an established M. tuberculosis H37Rv infection.
Figure 2: Elimination of residual M. tuberculosis by DNA vaccination after chemotherapy.

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Acknowledgements

This study was supported in part by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Financiadora de Estudos e Projetos (FINEP) and World Health Organization (WHO) Global Programme for Vaccination and Immunization.

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Authors and Affiliations

  1. Laboratory for Mycobacterial Research, National Institute for Medical Research, NW7 1AA, London, UK

    Douglas B. Lowrie, Ricardo E. Tascon, Evangelos Stavropoulos & M. Joseph Colston

  2. Department of Parasitology, Microbiology and Immunology, School of Medicine of Riberão Preto, Ribeirão Preto, 14049-900, São Paulo, Brazil

    Vania L. D. Bonato, Valeria M. F. Lima & Celio L. Silva

  3. Department of Clinical Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, São Paulo, Brazil

    Lucia H. Faccioli

  4. Central Veterinary Laboratory, New Haw, KT15 3NB, Addlestone, UK

    Robert G. Hewinson

  5. Institute of Medical Virology, University of Zurich, Gloriastrasse 30, CH-8028, Zurich, Switzerland

    Karin Moelling

Authors
  1. Douglas B. Lowrie
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  2. Ricardo E. Tascon
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  7. M. Joseph Colston
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  10. Celio L. Silva
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Correspondence to Celio L. Silva.

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Lowrie, D., Tascon, R., Bonato, V. et al. Therapy of tuberculosis in mice by DNA vaccination. Nature 400, 269–271 (1999). https://doi.org/10.1038/22326

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