WISCONSIN NATIONAL PRIMATE RESEARCH CENTER SUPPORT

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。 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HIV的人类一样，有限数量的猕猴（称为“精英控制者（EC）”）自发有效地控制SIV复制。最近，UW-Madison/WNPRC艾滋病疫苗研究实验室的研究人员在一组196只印度恒河猴中发现了16个EC。MHC I类等位基因的基因分型显示，这16个EC中有14个表达Mamu-B*17或Mamu-B*08，它们似乎分别是猕猴在人类中HLA-B57和HLA-B27的功能等同物。然而，对这些动物的监测和取样并不一致，这些动物通常是在不同研究人员进行的实验过程中确定的。此外，由于财政限制，动物往往必须在特定研究结束时安乐死。我们计划建立一个样本库，数据库，并容纳现有的和未来的EC猕猴在WNPRC。将这些独特的资源提供给从事SIV研究的调查人员社区，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保护免疫相关性的明确理解。因此，试图了解某些罕见个体（人类和猕猴）在未接种疫苗的情况下自然表现出保护作用的潜在机制是非常重要的。研究HIV复制的精英控制者（EC）是复杂的，因为额外的变量起作用，如病毒的异质性和无法知道感染的来源和时间。相比之下，非人灵长类动物模型研究允许通过采用单分子克隆病毒的病毒接种物的均匀性。

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.