Therapy of tuberculosis in mice by DNA vaccination

Mycobacterium tuberculosis continues to kill about 3 million people every year, 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 catastroph...

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Bibliographic Details
Published in:	Nature (London) Vol. 400; no. 6741; pp. 269 - 271
Main Authors:	Lowrie, Douglas B, Tascon, Ricardo E, Bonato, Vania L. D, Lima, Valeria M. F, Faccioli, Lucia H, Stavropoulos, Evangelos, Colston, M. Joseph, Hewinson, Robert G, Moelling, Karin, Silva, Celio L
Format:	Journal Article
Language:	English
Published:	London Nature Publishing 15-07-1999 Nature Publishing Group
Subjects:	Animals Antigens, Bacterial - genetics Antigens, Bacterial - immunology Antitubercular Agents - therapeutic use Bacterial diseases Bacterial Proteins Bacteriology Biological and medical sciences Chaperonin 60 Chaperonins - genetics Combined Modality Therapy Deoxyribonucleic acid DNA Experimental bacterial diseases and models Female Fundamental and applied biological sciences. Psychology Immune response Immune system Immunotherapy Infectious diseases Interferon-gamma - metabolism Interleukin-12 - secretion Interleukin-4 - metabolism Isoniazid - therapeutic use Medical sciences Mice Mice, Inbred BALB C Microbiology Mycobacterium leprae - genetics Mycobacterium tuberculosis Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - immunology Plasmids Pyrazinamide - therapeutic use Rodents T-Lymphocytes - immunology T-Lymphocytes - metabolism Tuberculosis Tuberculosis - immunology Tuberculosis - therapy Vaccines Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies Vaccines, DNA - immunology Vaccines, DNA - therapeutic use Animal model Respiratory disease Treatment efficiency Rodentia Mycobacterial infection Recombinant DNA Genetic vaccine Infection Vertebrata Mammalia Treatment Tuberculosis Mycobacterium tuberculosis Mouse Mycobacteriales Immunotherapy Bacteriosis Mycobacteriaceae Bacteria Actinomycetes
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Summary:	Mycobacterium tuberculosis continues to kill about 3 million people every year, 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 measure. In addition, effective treatment requires that patients take large doses of antibacterial drug combinations for at least 6 months after diagnosis, 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 chemotherapy. 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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0028-0836 1476-4687
DOI:	10.1038/22326