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Letters to Nature

Nature 400, 269-271 (15 July 1999) | doi:10.1038/22326; Received 14 April 1999; Accepted 18 May 1999

Open Innovation Challenges

Therapy of tuberculosis in mice by DNA vaccination

Douglas B. Lowrie1, Ricardo E. Tascon1, Vania L. D. Bonato2, Valeria M. F. Lima2, Lucia H. Faccioli3, Evangelos Stavropoulos1, M. Joseph Colston1, Robert G. Hewinson4, Karin Moelling5 & Celio L. Silva2

  1. Laboratory for Mycobacterial Research, National Institute for Medical Research, London NW7 1AA, UK
  2. Department of Parasitology, Microbiology and Immunology, School of Medicine of Riberão Preto, 14049-900, Ribeirão Preto, São Paulo, Brazil
  3. Department of Clinical Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo 14049-900, Ribeirão Preto, São Paulo, Brazil
  4. Central Veterinary Laboratory, New Haw, Addlestone KT15 3NB, UK
  5. Institute of Medical Virology, University of Zurich, Gloriastrasse 30, CH-8028 Zurich, Switzerland

Correspondence to: Correspondence and requests for materials should be addressed to C.L.S. (e-mail: Email: clsilva@beverly.fmrp.usp.br.)

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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.