MUCOSAL IMMUNITY TO SIV INFECTION AND VACCINES

对 SIV 感染和疫苗的粘膜免疫

• 批准号: 2004079
• 负责人: LAWRENCE A. WILSON
• 金额: $ 24.31万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-11-01 至 1998-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2004079
• 关键词: B lymphocyte; Macaca mulatta; Salmonella; cell mediated cytotoxicity; cellular immunity; cytotoxic T lymphocyte; disease /disorder model; enzyme linked immunosorbent assay; helper T lymphocyte; immunoglobulin A; immunoglobulin G; immunoglobulin M; immunologic assay /test; interleukin 4; interleukin 5; microorganism immunology; monocyte; mucosal immunity; plasma cells; polymerase chain reaction; recombinant proteins; simian immunodeficiency virus; viral vaccines

Unique aspects of the biology of HIV/SIV infection, including the use of immunologically functional CD4 as the receptor for infection of functional immune cells, the permanence of the infection due to integration into the host genome, and the mutability of these viruses pose great challenges for the development of a protective vaccine. Since a dominant protective immune mechanism remains unidentified, several potentially protective immune mechanisms must be considered and intensively studied simultaneously in order to fully understand the results of vaccine trials. Sexual transmission of cell-free an cell- associated virus to mucosal membranes is a major route of infection. Studies of mucosal immunity pose a particular problem because the process of mucosal infection and the mechanisms of immunity are not completely understood. Such studies are labor intensive and technically demanding, and require groups with diverse skills for their accomplishment. Two on- site groups will work in close collaboration to provide a comprehensive evaluation of systemic and mucosal immunity related to viral pathogenesis and protection. We will: 1) evaluated mucosal and systemic cell-mediated immunity including TH1/TH2 proportion and cytotoxic immune mechanisms such as cytotoxic T-lymphocytes (CTL), antibody-dependent cellular cytolysis (ADCC) and antibody complement cytotoxicity (ACC); 2) assess the induction of specific B-cells and plasma cells by various vaccines and adjuvants; and 3) compare different priming routes for induction of mucosal CTL. Through close interactions that have been established among these investigators, a composite view of the mucosal immune system should result from these studies.

HIV/SIV感染生物学的独特方面，包括使用 免疫功能性CD 4作为感染的受体 功能性免疫细胞，由于感染的持久性， 整合到宿主基因组中，以及这些病毒的突变性 对保护性疫苗的研发提出了巨大的挑战。 以来 一种占主导地位的保护性免疫机制仍然没有确定， 必须考虑潜在的保护性免疫机制， 同时深入研究，以充分了解 疫苗试验的结果。 无细胞的性传播- 粘膜相关病毒是主要的感染途径。 粘膜免疫的研究提出了一个特殊的问题，因为这个过程 粘膜感染和免疫机制还不完全 明白 这些研究是劳动密集型的，技术要求很高， 需要具备不同技能的团队来完成。 两个在- 网站小组将密切合作， 评价与病毒发病机制相关的全身和粘膜免疫 和保护. 我们将：1）评估粘膜和全身细胞介导的免疫 包括TH 1/TH 2比例和细胞毒性免疫机制， 细胞毒性T淋巴细胞（CTL），抗体依赖性细胞溶解 （ADCC）和抗体补体细胞毒性（ACC）; 2）评估细胞毒性。 通过各种疫苗诱导特异性B细胞和浆细胞， 佐剂;和3）比较不同的引发途径用于诱导 粘膜CTL 通过建立密切的互动， 这些研究人员认为，粘膜免疫系统的综合观点应该 这些研究的结果。

项目成果

Identification of SIV env-specific CTL in the jejunal mucosa in vaginally exposed, seronegative rhesus macaques (Macaca mulatta).

阴道暴露、血清阴性恒河猴 (Macaca mulatta) 空肠粘膜中 SIV env 特异性 CTL 的鉴定。

• DOI: 10.1034/j.1600-0684.2000.290311.x
• 发表时间: 2000
• 期刊: Journal of medical primatology
• 影响因子: 0.7
• 作者: Wilson,LA;Murphey-Corb,M;Martin,LN;Harrison,RM;Ratterree,MS;Bohm,RP
• 通讯作者: Bohm,RP

Selective induction of protective MHC class I-restricted CTL in the intestinal lamina propria of rhesus monkeys by transient SIV infection of the colonic mucosa.

通过结肠粘膜的短暂 SIV 感染，选择性诱导恒河猴肠固有层中保护性 MHC I 类限制性 CTL。

• 发表时间: 1999
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Murphey-Corb,M;Wilson,LA;Trichel,AM;Roberts,DE;Xu,K;Ohkawa,S;Woodson,B;Bohm,R;Blanchard,J
• 通讯作者: Blanchard,J