Novel therapeutic vaccine Granulysin and new DNA vaccine against tuberculosis

作者：Okada Masaji^*; Kita Yoko; Nakajima Toshihiro; Kanamaru Noriko; Hashimoto Satomi; Nagasawa Tetsuji; Kaneda Yasufumi; Yoshida Shigeto; Nishida Yasuko; Nakatani Hitoshi; Takao Kyoko; Kishigami Chie; Nishimatsu Shiho; Sekine Yuki; Inoue Yoshikazu; Matsumoto Makoto; McMurray David N; Dela Cruz E C; Tan E V; Abalos R M; Burgos J A; Saunderson Paul; Sakatani Mitsunori

来源：Human Vaccines, 2011, 7: 60-67.

DOI：10.4161/hv.7.0.14563

• Mycobacterium tuberculosis
• therapeutic vaccine
• HVJ-envelope
• monkey granulysin
• multi-drug resistant tuberculosis
• cytotoxic T cell
• IL-2
• mouse
• XDR-TB

Purpose: Multi-drug resistant (MDR) Mycobacterium tuberculosis (M. TB) is a big problem in the world. We have developed novel TB therapeutic vaccines.
Results and Methods: DNA vaccine expressing mycobacterial heat shock protein 65 and IL-12 was delivered by the hemagglutinating virus of Japan (HVJ)-envelope. M.TB, MDR-TB or extremenly drug resistant (XDR-TB) was injected i.v. into DBA/1 mice, and treated with the vaccine three times. This HVJ-E/Hsp65DNA+IL-12DNA vaccine provided strong therapeutic efficacy against MDR-TB and XDR-TB (prolongation of survival time and the decrease in the number of TB) in mice. Therapeutic effect of this vaccine on TB infection was also demonstrated in chronic TB infection murine model using aerosol infection intratracheally. On the other hand, granulysin protein produced from CTL has lethal activity against TB. Granulysin protein vaccine also exerted strong therapeutic effect. Furthermore, we extended our studies to monkey model, which is currently the best animal model of human TB. Hsp65DNA+IL-12 DNA vaccine exerted strong therapeutic efficacy (100% survival and augmentation of immune responses) in the TB-infected monkeys. In contrast, the survival of the saline control group was 60% at 16 week post-challenge. HVJ-Envelope/HSP65 DNA+IL-12 DNA vaccine increased the body weight of TB-infected monkeys, improved the erythrocyte sedimentation rate and augmentated the immune responses (proliferation of PBL and IL-2 production). The enhancement of IL-2 production from monkeys treated with this vaccine was correlated with the therapeutic efficacy of the vaccine.
Conclusion: These data indicate that novel vaccines might be useful against TB including XDR-TB and MDR-TB for human therapeutic clinical trials.

• 出版日期2011-2