Okada Masaji, Kita Yoko, Nakajima Toshihiro, Kanamaru Noriko, Hashimoto Satomi, Nagasawa Tetsuji, Kaneda Yasufumi, Yoshida Shigeto, Nishida Yasuko, Fukamizu Reiko, Tsunai Yoshie, Inoue Ruriko, Nakatani Hitoshi, Namie Yumi, Yamada Junko, Takao Kyoko, Asai Ritsuko, Asaki Ryoko, Matsumoto Makoto, McMurray David N, Dela Cruz E C, Tan E V, Abalos R M, Burgos J A, Gelber Robert, Sakatani Mitsunori
Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center,1180 Nagasone, Kitaku, Sakai, Osaka 591-8555, Japan.
Vaccine. 2007 Apr 20;25(16):2990-3. doi: 10.1016/j.vaccine.2007.01.014. Epub 2007 Jan 22.
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)-liposome (HSP65+IL-12/HVJ). This vaccine provided remarkable protective efficacy in mouse and guinea pig models compared to the BCG vaccine, on the basis of an induction of the CTL activity and improvement of the histopathological tuberculosis lesions, respectively. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. This novel vaccine provided a higher level of the protective efficacy than BCG based upon the assessment of mortality, the ESR, body weight, chest X-ray findings and immune responses. Furthermore, the combination of HSP65+IL-12/HVJ and BCG by the priming-booster method showed a synergistic effect in the TB-infected cynomolgus monkey (100% survival). These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis for human 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）-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）。与卡介苗相比，该疫苗在小鼠和豚鼠模型中分别基于CTL活性的诱导和组织病理学结核病变的改善提供了显著的保护效力。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。基于死亡率、血沉、体重、胸部X光检查结果和免疫反应的评估，这种新型疫苗比卡介苗提供了更高水平的保护效力。此外，通过初免-加强方法将HSP65+IL-12/HVJ与卡介苗联合使用在感染结核病的食蟹猴中显示出协同效应（100%存活）。这些数据表明，我们的新型DNA疫苗可能对结核分枝杆菌用于人类临床试验有用。
