WISCONSIN NATIONAL PRIMATE RESEARCH CENTER SUPPORT

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。 目的：了解控制艾滋病病毒复制的免疫学和遗传学基础，为疫苗设计提供依据。 与感染艾滋病毒的人类一样，数量有限的猕猴被称为“精英控制器(ECs)”，它们自发并有效地控制着SIV的复制。最近，华盛顿大学麦迪逊分校/WNPRC艾滋病疫苗研究实验室的研究人员在196只印度恒河猴队列中发现了16只ECs。对MHC I类等位基因的基因分型显示，在这16个EC中，有14个表达MAMU-B*17或MAMU-B*08，它们似乎分别与人类的HLAB57和HLAB27在功能上等同。然而，对这些动物的监测和采样通常是在不同的调查人员进行的实验过程中确定的，但并不一致。此外，由于资金紧张，动物往往必须在具体研究结束时实施安乐死。我们计划建立一个样本库，数据库，并在WNPRC容纳现有和未来的EC猕猴。将这些独特的资源提供给从事小岛屿发展中国家工作的研究人员群体，将是对该领域的一项极其宝贵的服务。艾滋病毒疫苗开发的最大障碍之一是缺乏对免疫相关因素的清楚了解，以进行保护。因此，试图了解某些稀有个体(包括人类和猕猴)在不接种疫苗的情况下自然表现出保护作用的潜在临床保护机制是非常重要的。研究艾滋病毒复制的精英控制器(ECs)由于其他变量的影响而变得复杂，例如病毒的异质性和无法知道感染源和感染的时间。相比之下，非人灵长类动物模型研究通过使用单个分子克隆病毒来实现病毒接种的一致性。

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. Objective: To understand the immunological and genetic basis of control of AIDS virus replication to help inform vaccine design. As in HIV-infected humans, a limited number of macaques, called "elite controllers (ECs)," spontaneously and effectively control SIV replication. Recently investigators in the UW-Madison/WNPRC AIDS Vaccine Research Lab identified sixteen ECs in a cohort of 196 Indian rhesus macaques. Genotyping for MHC class I alleles revealed that fourteen of these sixteen ECs expressed either Mamu-B*17 or Mamu-B*08, which appear to be the macaque functional equivalents of, in humans, HLA-B57 and HLA-B27, respectively. However, the monitoring and sampling of these animals, which were typically identified in the course of experiments run by different investigators, has not been consistent. Moreover, due to financial constraints, animals often must be euthanized at the end of specific studies. We plan to establish a sample bank, database, and to house existing and future EC macaques at the WNPRC. Making these unique resources available to the community of investigators working on SIV would be an extremely valuable service to the field. One of the biggest obstacles for HIV vaccine development is the lack of a clear understanding of the immune correlates for protection. Therefore, attempts to understand the potential mechanisms underlying apparent clinical protection in certain rare individuals (both human and macaque) who naturally exhibit protection without vaccination are highly significant. Studying elite controllers (ECs) of HIV replication is complicated by the fact that additional variables come into play, such as viral heterogeneity and the inability to know the source and timing of the infection. In contrast, nonhuman primate model studies allow uniformity of the viral inoculum by employing a single molecularly cloned virus.