ROLE OF VIRUS SPECIFIC IMMUNITY IN PRIMATE MODELS

病毒特异性免疫在灵长类动物模型中的作用

• 批准号: 8357408
• 负责人: Aftab A. Ansari
• 金额: $ 5.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357408
• 关键词: Animals; Antiviral Agents; CD8B1 gene; Cercocebus; Cercocebus atys; Chronic; Evaluation; Functional disorder; Funding; Grant; Immune; Immune response; Immunity; Immunization; Infection; Influenza; Interleukin-12; Interleukin-15; Interleukin-2; Interleukin-7; Interruption; Long-Term Effects; Macaca mulatta; Mediating; Memory; Modeling; Monitor; Monkeys; National Center for Research Resources; Potassium Channel; Primates; Principal Investigator; Protocols documentation; Regulatory T-Lymphocyte; Research; Research Infrastructure; Resources; Role; SIV; Source; Structure; T memory cell; T-Lymphocyte; United States National Institutes of Health; Viral Load result; Viremia; Virus; cell mediated immune response; chemotherapy; cost; cytokine; in vivo; inhibitor/antagonist; pinacolyl methylphosphonic acid

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. This project investigates the potential for cytokines promoting cell mediated immune responses for restoring/augmenting antiviral immune responses following SIV infection by administration of IL-12 alone or in combination with IL-2 or Il-15 and a structured antiviral chemotherapy interruption protocol using PMPA. The past year has been devoted primarily to the monitoring of the rhesus infected with SIVmac251 and treated with STI and IL-12. Surviving monkeys with variable levels of immune mediated control of the SIV viremia have been subjected to chronic administration of IL-15 followed by IL-7 to document the effect of these T cell directed cytokines on the viral loads and antiviral immune responses in vivo. In addition, parallel studies were initiated in sooty mangabeys in attempt to delineate T cell dysfunction in the pathogenic rhesus vs non pathogenic mangabey monkey. The role of regulatory T cells was investigated longitudinally in both models as well as the potential role of PD-1 expression on CD4 and CD8+ T cells. In addition, a preliminary evaluation of the in vivo administration of inhibitors of potassium channels specific for central memory and effector memory T cells was performed in conjunction with an immunization with influenza. The project is near its completion and the final four animals are being observed for longterm effects of the therapy.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 本项目通过单独或联合应用IL-12或IL-2或IL-15以及使用PMPA的结构化抗病毒化疗中断方案，研究了细胞因子促进细胞介导的免疫反应在SIV感染后恢复/增强抗病毒免疫反应的可能性。过去的一年主要用于监测感染SIVmac251并接受STI和IL-12治疗的恒河猴。免疫调节控制SIV病毒血症水平不同的存活猴子接受了IL-15和IL-7的长期注射，以证明这些T细胞导向的细胞因子对体内病毒载量和抗病毒免疫反应的影响。此外，在煤烟芒果猴中启动了平行研究，试图描述致病猕猴和非致病芒果猴的T细胞功能障碍。在这两个模型中，纵向研究了调节性T细胞的作用，以及PD-1在CD4和CD8+T细胞上的表达的潜在作用。此外，结合流感免疫，对中枢记忆和效应记忆T细胞特异性钾通道抑制剂的体内给药进行了初步评估。该项目即将完成，最后四只动物正在接受治疗的长期效果观察。