Wisconsin National Primate Research Center Support

威斯康星国家灵长类研究中心支持

• 批准号: 7904555
• 负责人: MARTIN CADWALLADER
• 金额: $ 92.15万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-17 至 2011-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904555
• 关键词: Wisconsin; National; Primate; Research; Center

DESCRIPTION (provided by applicant): Understanding the immunological and genetic basis of control of AIDS virus replication should help inform vaccine design. As in HIV-infected humans, a limited number of macaques spontaneously control SIV replication to less than 1,000 copies/ml after infection ("Elite Controllers"; ECs) (18, 32). This is a greater than two log reduction from the typical plasma virus load after challenge with SIVmac239. Recently we identified sixteen ECs in a cohort of 196 Indian rhesus macaques (18). 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 HLA-B57 and HLA-B27, respectively (2, 9, 12, 21, 26, 29). 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. Component Critique Significance: 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, NHP model studies allow uniformity of the viral inoculum by employing a single molecularly cloned virus

描述（由申请人提供）：了解控制艾滋病病毒复制的免疫学和遗传学基础应有助于为疫苗设计提供信息。与感染HIV的人类一样，有限数量的猕猴在感染后自发地将SIV复制控制在1，000拷贝/ml以下（“精英控制者”; EC）（18，32）。这比用SIVmac 239攻击后的典型血浆病毒载量减少了2个对数以上。最近，我们在一组196只印度恒河猴中鉴定出16只EC（18）。MHC I类等位基因的基因分型显示，这16个EC中的14个表达Mamu-B*17或Mamu-B*08，其似乎分别是HLA-B57和HLA-B27的猕猴功能等同物（2，9，12，21，26，29）。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。 组件批判 重要性：HIV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，尝试了解某些在未接种疫苗的情况下自然表现出保护作用的罕见个体（人类和猕猴）明显临床保护的潜在机制非常重要。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，NHP模型研究通过采用单分子克隆病毒来实现病毒接种物的均匀性