R5 SHIV/MACAQUE MODEL FOR THE EVALUATION OF T AND B CELL-BASED HIV-1 VACCINE

用于评估基于 T 细胞和 B 细胞的 HIV-1 疫苗的 R5 SHIV/猕猴模型

• 批准号: 8173045
• 负责人: CECILIA C CHENG-MAYER
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173045
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Animal Model; Biological Models; CD4 Positive T Lymphocytes; Cells; Computer Retrieval of Information on Scientific Projects Database; Evaluation; Funding; Grant; Gut associated lymphoid tissue; HIV-1; Human; Immune system; Infection; Institution; Macaca; Modeling; Pathogenicity; Process; Reporting; Research; Research Personnel; Resources; Route; Source; T-Cell Depletion; United States National Institutes of Health; Vaccines; Viremia; Virus Replication; arm; base; in vivo; preference; rectal; transmission process; vaccine candidate

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. We recently reported high levels of virus replication, acute CD4+ T cell depletion in the gut associated lymphoid tissues (GALT), and coreceptor switch in Indian (Ind) RMs infected intravenously (IV) with the late R5 tropic SHIVSF162P3N isolate. To more closely mimic the common modes of transmission of HIV-1 in humans, infection though the rectal route of SHIVSF162P3N was examined. In Preliminary studies, we show that mucosal infection of Ind RMs with R5 SHIVSF162P3N recapitulates key pathogenic features of HIV-1 infection in humans including acute CD4+ T cell depletion in the gut, uncontrolled replication, and progression to AIDS with switch in coreceptor preference. The consistency of high setpoint viremia and pathogenicity seen in SHIVSF162P3N IV and IR infected macaques leads us to hypothesize that this animal model system will be highly relevant not only for in-depth studies of the evolutionary process and the underlying mechanism for the change in coreceptor preference in vivo, but also for advancing the discovery of HIV-1 candidate vaccines that stimulate both effector arms of the immune system.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们最近报道了在静脉内 (IV) 感染晚期 R5 热带 SHIVSF162P3N 分离株的印度 (Ind) RM 中，病毒复制水平较高、肠道相关淋巴组织 (GALT) 中急性 CD4+ T 细胞耗竭以及辅助受体转换。为了更接近地模拟人类中 HIV-1 的常见传播模式，对 SHIVSF162P3N 的直肠途径感染进行了检查。在初步研究中，我们表明，R5 SHIVSF162P3N 的 Ind RM 粘膜感染概括了人类 HIV-1 感染的关键致病特征，包括肠道中 CD4+ T 细胞的急性耗竭、不受控制的复制以及随着共受体偏好的转变而进展为 AIDS。在 SHIVSF162P3N IV 和 IR 感染的猕猴中观察到的高设定点病毒血症和致病性的一致性使我们假设该动物模型系统不仅对于深入研究进化过程和共同受体偏好变化的潜在机制具有高度相关性体内，还促进了刺激免疫系统两个效应臂的 HIV-1 候选疫苗的发现。