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。 全球HIV-1疫苗设计的一个主要障碍是病毒多样性。目前，数据表明，包含单一抗原的疫苗将无法产生广泛反应的B细胞和T细胞反应，从而能够针对不同的HIV-1毒株提供保护。我们专注于HIV-1疫苗鸡尾酒策略，受到其他领域鸡尾酒疫苗成功的推动。多载体、多包膜疫苗策略诱导HIV-1特异性B细胞和T细胞功能(通过抗体结合、中和、抗体依赖细胞介导的细胞毒性和伽马干扰素检测来衡量)，具有预防人类感染HIV-1所需的多样性和持久性。基于TNPRC以前的疫苗研究的成功，在这项研究中，我们比较了3种疫苗方案与未接种疫苗的对照动物的效果。用部分或全部DNA、活的和灭活的表达HIV-env的重组牛痘病毒和HIV蛋白的组合接种动物。细胞和体液免疫反应的体外研究表明，在多次接种后，对SHV有强烈的、广泛的免疫反应。用SIV对动物进行挑战，以评估体内疫苗的效力。临床结果显示，接种疫苗的猴子有明显的保护作用，6只未接种疫苗的对照组中有4只，只有1只接种了因SHV相关疾病而实施安乐死的动物。病毒载量数据尚待公布。

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.