HIV VACCINE RATIONALE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 今年，我们研究了与发现成功的HIV-1疫苗有关的两个问题。通过实验1，我们解决了关于免疫缺陷病毒诱导保护性免疫反应的能力的重要辩论。通过实验2，我们测试了多载体(DNA、痘苗病毒、蛋白质)、多包膜HIV-1疫苗抵御异种SIV攻击的能力。方法：实验一，两只猕猴接种新城疫病毒KU-1，休息10个月后暴露于新城疫病毒89.6P。这项实验是在2008年之前进行的，但评估工作已于今年完成。在实验2中，几组猕猴接种了多载体、多包膜的疫苗。一些动物接种了被紫外线灭活的牛痘病毒。实验动物和对照动物分别用SIV 89.6P进行攻击。结果：在实验1中，我们发现SHV KU-1感染后可诱导多种中和抗体活性，并在E10个月期间有所改善。在暴露于新城疫病毒89.6P后，所有对照动物均被感染，大多数动物死于疾病。相比之下，在实验动物中，一只没有显示出重复感染的证据，第二只只在一个时间点显示出病毒。两种动物都没有表现出疾病的迹象。实验2表明，多囊膜疫苗对疾病有保护作用，痘苗病毒重组载体在灭活后仍具有免疫原性。讨论：实验1清楚地表明，受感染的动物可以对重复感染产生保护性免疫反应。我们认为，这种保护状态可以作为HIV-1疫苗开发的“黄金标准”，因为对人类免疫缺陷病毒感染的类似程度的保护将是非常理想的。实验2展示了多包膜疫苗的效力，同时验证了一种可能用于未来临床试验的载体修改，以确保HIV-1疫苗的安全性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This year, we examined two issues pertinent to the discovery of a successful HIV-1 vaccine. With experiment 1, we addressed an important debate concerning the ability of an immunodeficiency virus to elicit a protective immune response. With experiment 2 we tested the ability of a multi-vectored (DNA, vaccinia virus, protein), multi-envelope HIV-1 vaccine to protect against a heterologous SHIV challenge. Methods: In experiment 1, two macaques received an inoculation with SHIV KU-1 and were rested for 10 months, after which animals were exposed to SHIV 89.6P. This experiment was conducted prior to 2008, but evaluation was completed this year. In experiment 2, groups of macaques received multi-vectored, multi-envelope vaccines. Some animals received vaccinia virus that had been inactivated by ultra-violet light. Test and control animals were challenged with SHIV 89.6P. Results: In experiment 1, we found that SHIV KU-1 infection elicited diverse neutralizing antibody activities that improved during the e10 month period. After exposure to SHIV 89.6P, all control animals were infected and most succumbed to disease. In contrast, among test animals, one showed no evidence of superinfection and the second showed virus at only one time point. Neither animal showed signs of disease. Experiment 2 showed that the multi-envelope vaccine protected against disease and that the vaccinia virus recombinant vector was immunogenic even after inactivation. Discussion: Experiment 1 clearly demonstrated that infected animals could mount a protective immune response against superinfection. We suggest that this protective state may serve as a 'gold-standard' for HIV-1 vaccine development, as a similar degree of protection against immunodeficiency virus infections in humans would be much desired. Experiment 2 demonstrated the potency of a multi-envelope vaccine, while validating a vector modification that might be used in future clinical trials to ensure HIV-1 vaccine safety.