Okada Masaji, Kita Yoko, Nakajima Toshihiro, Kanamaru Noriko, Hashimoto Satomi, Nagasawa Tetsuji, Kaneda Yasufumi, Yoshida Shigeto, Nishida Yasuko, Nakatani Hitoshi, Takao Kyoko, Kishigami Chie, Inoue Yoshikazu, Matsumoto Makoto, McMurray David N, Dela Cruz E C, Tan E V, Abalos R M, Burgos J A, Saunderson Paul, Sakatani Mitsunori
Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center, 1180 Nagasone, Kitaku, Sakai, Osaka 591-8555, Japan.
Vaccine. 2009 May 26;27(25-26):3267-70. doi: 10.1016/j.vaccine.2009.01.064. Epub 2009 Feb 5.
We have developed a novel tuberculosis (TB) vaccine; a combination of the DNA vaccines expressing mycobacterial heat shock protein 65 (HSP65) and interleukin 12 (IL-12) delivered by the hemagglutinating virus of Japan (HVJ)-envelope and -liposome (HSP65+IL-12/HVJ). This vaccine provided therapeutic efficacy as well as remarkable protective efficacy via CD8(+) T and CD4(+) T cells in murine models compared with the saline controls, on the basis of CFU of number of multi-drug resistant TB (MDR-TB), and survival of extremely drug resistant TB (XDR-TB) challenged mice. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. This vaccine exerted therapeutic efficacy (survival and immune responses) in the TB-infected monkeys. These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis including XDR-TB and MDR-TB for human therapeutic clinical trials.
我们研发了一种新型结核病（TB）疫苗；一种由日本血凝病毒（HVJ）包膜和脂质体递送的、表达分枝杆菌热休克蛋白65（HSP65）和白细胞介素12（IL-12）的DNA疫苗组合（HSP65+IL-12/HVJ）。与生理盐水对照组相比，该疫苗在小鼠模型中通过CD8(+) T细胞和CD4(+) T细胞提供了治疗效果以及显著的保护效果，这是基于耐多药结核病（MDR-TB）的菌落形成单位数量以及极耐多药结核病（XDR-TB）攻击小鼠的存活率得出的。此外，我们将研究扩展到了食蟹猴模型，其目前是人类结核病的最佳动物模型。该疫苗在感染结核病的猴子中发挥了治疗效果（存活率和免疫反应）。这些数据表明，我们的新型DNA疫苗可能对包括XDR-TB和MDR-TB在内的结核分枝杆菌用于人类治疗性临床试验有用。
