PILOT PROJECT FOR LIVE ATTENUATED VACCINE IMMUNE CORRELATES - IAVI

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。 该项目旨在试行盖茨基金会/IAVI大型合作项目“非人灵长类(NHP)减毒活疫苗(LAV)免疫关联”项目所需的方法和程序，并提供初步的“关联”数据，用于确定这些方法的优先顺序。整个研究的目的是描述宿主先天和/或获得性免疫反应的特征，这些反应能够保护恒河猴免受病理性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开始，即恒河猴减毒活疫苗模型，并确定与这种保护相关的免疫参数。因此，该项目的最终计划是用已知提供完全SIV保护的SIV减毒活疫苗以及其他提供部分保护的LAV和非LAV方法(包括正在大规模临床试验中评估的Prime-Boost DNA/腺病毒方案)为恒河猴免疫。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。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。120只动物将被用于这项工作，以实现揭示复杂相关性的统计能力。这一试点项目的具体目标是使用已有的SIV(Delta-nef)疫苗接种恒河猴，在攻击前和攻击后立即优化LAV疫苗接种猴子的免疫学、病毒学和基因表达分析。

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 project is intended to pilot approaches and procedures necessary to carry out the large cooperative Gates Foundation/IAVI "Nonhuman Primate (NHP) Live Attenuated Vaccine (LAV) Immune Correlates" project (which is pending), and to provide preliminary "correlates" data that will be used to prioritize these approaches. The overall 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 in rhesus macaques  and determine the immune parameters that correlate with this protection. The ultimate plan of the 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 (including a prime-boost DNA/adenovirus regimen under evaluation in large-scale clinical trials). 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. Factors that best correlate with protection will be validated in further collaborative studies in macaques using a more stringent heterologous pathogenic SIV challenge. 120 animals will be used in this endeavor to achieve the statistical power to reveal complex correlates. The specific goals of this pilot project are to optimize immune, virologic and gene expression analysis of LAV-vaccinated monkeys in the pre- and immediate post-challenge period using pre-existing SIV(delta-nef) vaccinated rhesus macaques.