IMMUNOGENICITY OF HSV AMPLICONS IN RHESUS MACAQUES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。预防人类免疫缺陷病毒(HIV)感染的最佳战略包括开发有效的疫苗。单纯疱疹病毒(HSV)扩增片段代表了一种新的、有前途的疫苗开发策略。这项建议中描述的研究将确定HSV扩增片段是否能在恒河猴中引发显著的免疫反应。具体地说，恒河猴将通过肌肉注射途径接种表达复制缺陷SIVmax 239基因组的HSV扩增片段，或通过不表达任何SIV基因产物的对照扩增片段进行接种。对SIV蛋白的细胞免疫反应将通过分析CD4+和CD8+T细胞反应、四聚体染色和抗原特异性细胞因子产生来跟踪。体液反应将通过血清和粘膜免疫分析来确定。最后，将通过对自然杀伤细胞的分析和对淋巴细胞增殖和激活变化的纵向研究来确定先天免疫反应。

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. The best strategy for prevention of human immunodeficiency virus (HIV) infection involves the development of an effective vaccine. Herpes simplex virus (HSV) amplicons represent a novel and promising strategy for vaccine development. The studies described in this proposal will determine if HSV amplicons can elicit a significant immune response in the rhesus macaque. Specifically, rhesus macaques will be inoculated via an intramuscular route with HSV amplicons that express a replication-defective SIvmax239 genome or by control amplicons that do not express any SIV gene products. The cellular immune response to SIV proteins will be followed through analysis of CD4+ and CD8+ T cell responses, tetramer staining, and antigen-specific cytokine production. The humoral response will be determined by analysis of both serum and mucosal immunity. Finally, the innate immune response will be determined through analysis of both natural killer cells and by performing longitudinal studies of changes in lymphocyte proliferation and activation.