HIV VACCINE RATIONALE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 设计全球HIV-1疫苗的一个主要障碍是病毒的多样性。目前，数据表明，包含单一抗原的疫苗将不能产生广泛反应性的B细胞和T细胞应答，这些应答能够赋予针对HIV-1的不同分离株的保护。我们专注于HIV-1疫苗鸡尾酒策略，这是由鸡尾酒疫苗在其他领域的成功所推动的。多载体、多包膜疫苗策略增强了HIV-1特异性B和T细胞功能（通过抗体结合、中和、抗体依赖性细胞介导的细胞毒性和γ干扰素测定来测量），具有预防人类HIV-1感染所需的多样性和持久性。 基于TNPRC先前疫苗研究的成功，在本研究中，我们比较了3种疫苗方案与未接种对照动物的有效性。 用DNA、表达HIV-env的活的和灭活的重组牛痘病毒和HIV蛋白中的一些或全部的组合对动物进行疫苗接种。 在体外研究测量细胞和体液免疫反应表明，一个强大的，广泛的基础免疫反应，SHIV多次接种后。 用SHIV攻击动物以评估疫苗体内效力。 临床结果显示，在接种疫苗的猴中有明显的保护作用，6只未接种疫苗的对照动物中有4只，只有1只接种疫苗的动物因SHIV相关疾病而被安乐死。 病毒载量数据待定。

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. A major obstacle to the design of a global HIV-1 vaccine is viral diversity. At present, data suggest that a vaccine comprising a single antigen will fail to generate broadly reactive B-cell and T-cell responses able to confer protection against the diverse isolates of HIV-1. We focus on an HIV-1 vaccine cocktail strategy, prompted by cocktail vaccine successes in other fields. The multi-vectored, multi-envelope vaccine strategy elicits HIV-1-specific B- and T-cell functions (measured by antibody binding, neutralization, antibody-dependent cell-mediated cytotoxicity and gamma interferon assays), with a diversity and durability that may be required to prevent HIV-1 infections in humans. Based on the success of previous vaccine studies at TNPRC, in this study we are comparing the efficacy of 3 vaccine protocols to unvaccinated control animals. Animals were vaccinated with a combination of some or all of DNA, live and killed recombinant vaccinia virus expressing HIV-env, and HIV protein. In vitro studies measuring cellular and humoral immune response indicated a strong, broadly based immune response to SHIV following multiple vaccinations. Animals were challenged with SHIV to assess vaccine efficacy in vivo. Clinical findings show a clear protective effect in vaccinated monkeys with 4 of 6 unvaccinated controls and only one vaccinated animal euthanized for SHIV related disease. Viral load data is pending.