Therapy of tuberculosis in mice by DNA vaccination

Douglas B. Lowrie, Ricardo E. Tascon, Vania L.D. Bonato, Valeria M.F. Lima, Lucia H. Faccoli, Evangelos Stavropoulos, M. Joseph Colston, Robert G. Hewinson, Karin Moelling, Celio L. Silva*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

421 Citations (SciVal)

Abstract

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-Guerin (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.

Original languageEnglish
Pages (from-to)269-271
Number of pages3
JournalNature
Volume400
Issue number6741
DOIs
Publication statusPublished - 15 Jul 1999

Keywords

  • Animals
  • Antigens, Bacterial/genetics
  • Antitubercular Agents/therapeutic use
  • Bacterial Proteins
  • Chaperonin 60
  • Chaperonins/genetics
  • Combined Modality Therapy
  • Female
  • Interferon-gamma/metabolism
  • Interleukin-12/metabolism
  • Interleukin-4/metabolism
  • Isoniazid/therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium leprae/genetics
  • Mycobacterium tuberculosis/genetics
  • Plasmids
  • Pyrazinamide/therapeutic use
  • T-Lymphocytes/immunology
  • Tuberculosis/immunology
  • Vaccines, DNA/immunology

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