Therapy of tuberculosis in mice by DNA vaccination

Douglas B. Lowrie, Ricardo E. Tascon, Vania L. D. Bonato, Valeria M. F. Lima, Lucia H. Faccioli, Evangelos Stavropoulos, M. Joseph Colston, Robert G. Hewinson, Karin Moelling and Celio L. Silva ()
Additional contact information
Douglas B. Lowrie: Laboratory for Mycobacterial Research, National Institute for Medical Research
Ricardo E. Tascon: Laboratory for Mycobacterial Research, National Institute for Medical Research
Vania L. D. Bonato: Microbiology and Immunology, School of Medicine of Riberão Preto
Valeria M. F. Lima: Microbiology and Immunology, School of Medicine of Riberão Preto
Lucia H. Faccioli: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo
Evangelos Stavropoulos: Laboratory for Mycobacterial Research, National Institute for Medical Research
M. Joseph Colston: Laboratory for Mycobacterial Research, National Institute for Medical Research
Robert G. Hewinson: Central Veterinary Laboratory
Karin Moelling: Institute of Medical Virology, University of Zurich
Celio L. Silva: Microbiology and Immunology, School of Medicine of Riberão Preto

Nature, 1999, vol. 400, issue 6741, 269-271

Abstract: 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.

Date: 1999
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DOI: 10.1038/22326

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