IMMUNE CORRELATES OF PROTECTION AGAINST SIV INFECTION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项研究旨在描述宿主先天和/或获得性免疫反应的特征，这些免疫反应能够保护恒河猴免受病原性SIV感染，进而防止人类感染HIV-1。为了实现这一目标，我们将从疫苗诱导保护的最佳特征模型-猕猴减毒活疫苗模型(LAV)-开始，并确定与这种保护相关的免疫参数。因此，该项目的计划是用已知可提供完全SIV保护的SIV减毒活疫苗以及提供部分保护的其他LAV和非LAV方法来免疫恒河猴。然后，我们将生成一个全面的数据矩阵配置文件，比较接种疫苗的动物的免疫学、病毒学和遗传参数，并将这些参数与抵御高致病性同源SIV攻击的保护关联起来。这将是恒河猴SIV模型中最全面的免疫分析，包括对两种先天免疫的全面评估 (使用基因阵列技术)和适应性免疫(细胞和体液)，以及确定保护的遗传和病毒学成分。与保护最相关的因素将在使用更严格的异源致病SIV挑战对猕猴进行的进一步合作研究中得到验证。在过去的一年里，我们完成了对队列1的分析，一个由32个RM组成的小组接受了不同的LAV，以创建一个免疫相关矩阵：即广泛的免疫反应测量和致病SIV攻击后的不同结果，从而能够对免疫相关性进行统计分析。在这个队列中，我们发现了与周围淋巴结中SIV特异性T细胞反应的大小有关的预测结果的强烈统计信号，而不是其他部位。目前的工作旨在了解这种相关性的机制。目前正在准备一份描述这些发现的手稿。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This study is designed to characterize host innate and/or adaptive immune responses that have the capacity to protect against pathogenic SIV infection in rhesus macaques, and by extension, HIV-1 infection of humans. To accomplish this goal we will start with the best characterized model of vaccine-induced protection - the live attenuated vaccine model (LAV) in rhesus macaques - and determine the immune parameters that correlate with this protection. The plan of this project is therefore to immunize rhesus macaques with a live attenuated SIV vaccine known to provide complete SIV protection as well as with other LAV and non-LAV approaches that provide partial protection. We will then generate a comprehensive data matrix profile comparing the immunologic, virologic and genetic parameters of vaccinated animals and correlate these parameters with protection from highly pathogenic homologous SIV challenge. This will be the most comprehensive immune analysis in the rhesus macaque - SIV model, including comprehensive assessment of both innate (using gene array technology) and adaptive immunity (cellular and humoral), and determination of the genetic and virologic components of protection. Factors that best correlate with protection will be validated in further collaborative studies in macaques using a more stringent heterologous pathogenic SIV challenge. In the last year we have completed analysis of cohort #1, a group of 32 RM administered different LAVs so as to create an immune correlates matrix: that is, a broad spectrum of immune response measurements and different outcomes after pathogenic SIV challenge, so as to allow statistical analysis of immune correlates. In this cohort, we found a strong statistical signal with regard to prediction of outcome with the magnitude of SIV-specific T cell responses in peripheral lymph node but not other sites. Current work is directed at understanding the mechanisms of this correlation. A manuscript describing these findings is currently being prepared.