Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA pins protein vaccination
Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA pins protein vaccination
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DOI：
10.1073/pnas.94.17.9378
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发表时间：
1997-08-19
影响因子：
11.1
通讯作者：
Shiver, JW
中科院分区：
文献类型：
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作者：
Letvin, NL;Montefiori, DC;Shiver, JW
一般认为，预防HIV-1感染的有效疫苗应同时引起强中和抗体和细胞毒性T淋巴细胞应答。我们最近证明，使用质粒编码的HIV-1包膜（Env）DNA作为免疫原，可以在恒河猴中引起有效的、可加强的、长寿命的HIV-1包膜特异性细胞毒性T淋巴细胞应答。我们表明，将HIV-1 Env蛋白作为加强免疫原加入到该方案中，在该非人灵长类物种中产生高滴度的中和抗体应答。此外，我们在一项初步研究中证明，用HIV-1 env DNA免疫，（多次给药），然后用HIV-1 Env DNA加HIV-1 Env蛋白进行最终免疫（来自HIV IIIB的HXBc 2克隆的env基因;来自亲本HIV IIIB的Env蛋白）在用在猿猴免疫缺陷病毒（mac）骨架上表达HIV-1 env（HXBc 2）的嵌合病毒静脉内攻击后完全保护猴子免受感染（SHIV-HXBc2）.在这些试验性实验中观察到的有效免疫和保护表明，DNA初免/DNA加蛋白质加强方案值得积极研究，作为预防HIV-1感染的疫苗策略。
It is generally thought that an effective vaccine to prevent HIV-1 infection should elicit both strong neutralizing antibody and cytotoxic T lymphocyte responses, We recently demonstrated that potent, boostable, long-lived HIV-1 envelope (Env)-specific cytotoxic T lymphocyte responses can be elicited in rhesus monkeys using plasmid-encoded HIV-1 env DNA as the immunogen, In the present study, we show that the addition of HIV-I Env protein to this regimen as a boosting immunogen generates a high titer neutralizing antibody response in this nonhuman primate species, Moreover, we demonstrate in a pilot study that immunization with HIV-1 env DNA (multiple doses) followed by a final immunization with HIV-1 env DNA plus HIV-1 Env protein (env gene from HXBc2 clone of HIV IIIB; Env protein from parental HIV IIIB) completely protects monkeys from infection after i.v. challenge with a chimeric virus expressing HIV-1 env (HXBc2) on a simian immunodeficiency virus(mac) backbone (SHIV-HXBc2). The potent immunity and protection seen in these pilot experiments suggest that a DNA prime/DNA plus protein boost regimen warrants active investigation as a vaccine strategy to prevent HIV-1 infection.