NOVEL VACCINES AGAINST M. TUBERCULOSIS

DOI Web Site 1 Citations 10 References
  • OKADA Masaji
    Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center

Bibliographic Information

Other Title
  • 新しい結核ワクチン
  • ダイ81カイ ニホン ケッカクビョウ ガッカイ ソウカイ キョウイク コウエン アタラシイ ケッカク ワクチン

Search this article

Abstract

CDC and ACET in U. S. A. reported that novel vaccines instead of BCG are required for the protection against infection of Mycobacterium tuberculosis worldwide. However, no novel vaccine for clinical use has not yet been developed in the world including U. S. A. and Europe.<BR>We have developed two novel tuberculosis (TB) vaccines; a DNA vaccine combination expressing mycobacterial heat shock protein 65 (HSP 65) and interleukin-12 (IL-12) by using the hemagglutinating virus of Japan (HVJ)-liposome (HSP 65 +IL-12/HVJ). A mouse IL-12 expression vector (mIL-12 DNA) encoding single-chain 1L-12 proteins comorised of p40 and p35 subunits were constructed. In a mouse model, a single gene gun vaccination with the combination of HSP 65 DNA and mIL-12 DNA provided a remarkably high degree of protection against challenge with virulent Mycobacterium tuberculosis; bacterial numbers were 100 fold lower in the lungs compared to BCG-vaccinated mice. To explore the clinical use of the DNA vaccines, we evaluated HVJ-liposome encapsulated HAP 65 DNA and mIL-12 DNA (HSP 65 + mIL-12/ HVJ). The HVJ-liposome method improved the protective efficacy of the HSP 65 DNA vaccine compared to gene gun vaccination. This vaccine provide remarkable protective efficacy in mouse and guinea pig models, as compared to the current by available BCG vaccine. HSP 65 +1L-12/HVJ vaccine induced CD8 + cytoxic T lymphocyte activity against HSP 65 antigen. Protective efficacy of this vaccine was associated with the emergence of IFN- γ - secreting T cells and activation of proliferative T cells as well as CTL induction upon stimulation with the HSP 65 and antigens from M. tuberculosis. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis, to evaluate the HSP 65 +IL-12 /HVJ vaccine. Vaccination with HSP 65 +IL-12/HVJ provided better protective efficacy as assessed by the Erythrocyte Sedimentation Rate, chest X-ray findings, and immune responses than BCG. Most importantly, HSP 65 -FIL-12/HVJ resulted in an increased survival for over a year. This is the first report of successful DNA vaccination against M. tuber culosis in the monkey model. Novel TB vaccines using the monkey model will be discussed in this issue.

Journal

Citations (1)*help

See more

References(10)*help

See more

Keywords

Details 詳細情報について

Report a problem

Back to top