IN VIVO EVALUATION OF PRIMATE LENTIVIRUSES

灵长类慢病毒的体内评估

• 批准号: 8357593
• 负责人: DAVID M ANDERSON
• 金额: $ 37.79万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357593
• 关键词: Cells; Chemokine (C-C Motif) Receptor 5; Chinese People; Dose; Evaluation; Funding; Future; Grant; HIV-1; Human; Immune response; Infection; Intestines; Macaca; Macaca mulatta; Measures; Molecular Cloning; National Center for Research Resources; Pathogenicity; Peripheral; Peripheral Blood Mononuclear Cell; Primate Lentiviruses; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Route; Source; Subfamily lentivirinae; T-Lymphocyte; Testing; Therapeutic; United States National Institutes of Health; Vaccines; Virus; cost; design; env Genes; in vivo; lymph nodes; microbicide; nonhuman primate; simian human immunodeficiency virus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. When strains of lentiviruses become available, it is important to determine the infectivity, pathogenicity, and minimal infectious dose of each virus in a particular nonhuman primate species before it can be used in vaccine trails or therapeutic testing. This project is designed to allow lentiviruses to be tested in vivo. Simian-Human Immunodeficiency Virus-SF162P4 (SHIV SF162P4) is derived from a molecular clone, SHIV SF162, a chimeric virus that contains the env gene of a CCR-5-using primary isolate of subtype B HIV-1. A macaque-passaged stock, SHIV SF162P3 was found to cause a dramatic loss of intestinal T cells followed by a gradual depletion of peripheral T cells. Lymph node cells and PBMC from a macaque infected with the SHIV SF162P3 virus two weeks after infection were amplified in human PBMC to generate a P4 stock virus and a challenge stock was prepared. The current study was undertaken to measure the infectivity and inductive ability of B- and T-cell immune responses by the intravaginal route so that these SHIVs may serve as challenge viruses in future vaccine studies and microbicide trials in Chinese rhesus macaques utilizing this route of infection.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 当慢病毒株可用时，在将其用于疫苗试验或治疗测试之前，确定每种病毒在特定非人类灵长类动物中的感染性、致病性和最小感染剂量非常重要。 该项目旨在对慢病毒进行体内测试。 猿猴人类免疫缺陷病毒-SF162P4 (SHIV SF162P4) 源自分子克隆 SHIV SF162，这是一种嵌合病毒，包含使用 CCR-5 的 B 亚型 HIV-1 初级分离株的 env 基因。 猕猴传代的 SHIV SF162P3 被发现会导致肠道 T 细胞急剧减少，随后外周 T 细胞逐渐耗尽。 感染后两周感染 SHIV SF162P3 病毒的猕猴的淋巴结细胞和 PBMC 在人 PBMC 中扩增，产生 P4 母病毒，并制备攻击母病毒。 目前的研究旨在通过阴道内途径测量B细胞和T细胞免疫反应的感染性和诱导能力，以便这些SHIV可以作为未来利用这种感染途径在中国恒河猴中进行疫苗研究和杀菌剂试验的攻击病毒。