Evaluation of a novel vaccine (HVJ-liposome/HSP65 DNA+IL-12 DNA) against tuberculosis using the cynomolgus monkey model of TB
Evaluation of a novel vaccine (HVJ-liposome/HSP65 DNA+IL-12 DNA) against tuberculosis using the cynomolgus monkey model of TB
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DOI：
10.1016/j.vaccine.2007.01.014
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发表时间：
2007-04-20
期刊：
影响因子：
5.5
通讯作者：
Sakatani, Mitsunori
中科院分区：
文献类型：
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作者：
Okada, Masaji;Kita, Yoko;Sakatani, Mitsunori
我们开发了一种新型结核病疫苗；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，由日本血凝病毒 (HVJ)-脂质体 (HSP65 + IL-12/HVJ) 递送。与卡介苗疫苗相比，该疫苗在小鼠和豚鼠模型中提供了显着的保护功效，分别基于诱导 CTL 活性和改善组织病理学结核病灶。此外，我们将研究扩展到食蟹猴模型，这是目前最好的人类结核病动物模型。根据对死亡率、ESR、体重、胸部 X 光检查结果和免疫反应的评估，这种新型疫苗提供了比卡介苗更高水平的保护功效。此外，通过启动-加强方法联合使用HSP65+IL-12/HVJ和BCG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 疫苗可能有助于针对结核分枝杆菌进行人体临床试验。 (c) 2007 Elsevier Ltd. 保留所有权利。
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. (c) 2007 Elsevier Ltd. All rights reserved.