MUCOSAL AND SYSTEMIC IMMUNITY TO SIV AND HIV ANTIGENS

这项研究的总体目标是开发疫苗， 雄性和雌性猕猴生殖器SIV传播。 保护 在猕猴中进行的对抗SIV静脉内攻击的研究已经 成功，但人类艾滋病毒疫苗还必须保护免受 异性感染途径。 在我们之前的NCVDG研究中，女性 保护猕猴免受阴道攻击。 保护是 当动物用福尔马林处理的SIV免疫时， 生物可降解微球仅在肌内引发并通过 口服（OR）或肠内（IT）途径。 或者单独免疫并不能 保护。 这些数据表明，微球可能作为一种基本的疫苗 预防艾滋病毒阴道传播战略。 此续订 应用开发基于微球的疫苗和其他策略， 防止异性性传播，使用以下具体措施 目的： 目标1。 确定三种免疫策略中的最佳策略， 诱导阴道抗体，并确定哪种策略最适合 对阴道SIV攻击的保护。 这三个战略是 仅肌内（IM）免疫，IM引发加OR加强和IM 启动和IT提升。 目标2. 为了测试由表达的SIV组成的重组SIV制剂， 用于诱导阴道IgG和伊加水平的微球中的蛋白， 与我们以前用整个SIV微球的结果相当 免疫接种。 我们还将确定这些SIV重组体， 保护微球免疫的动物免受阴道攻击。 目标3。 制备阴道SIV浓缩抗体，用于检测其 在中和和其他免疫学测定中起作用。 目标4。 比较大腿和手臂肌肉作为肌内免疫 用于引发SIV阴道免疫诱导的位点。 目标5。 使用HIV在猕猴中进行免疫原性研究 用于诱导阴道和全身免疫的重组抗原。 目标6。 建立可靠的SIV雄性生殖器攻毒体系。

The overall goal of this study is to develop vaccines that will protect male and female macaques from genital SIV transmission. Protection studies in macaques against intravenous challenges with SIV have been successful, but HIV vaccines for humans must also protect against a heterosexual route of infection. In our previous NCVDG studies, female macaques were protected against vaginal challenges. Protection was achieved when animals were immunized with formalin-treated SIV in biodegradable microspheres only if primed intramuscularly and boosted by oral (OR) or intratracheal (IT) routes. OR immunization alone did not protect. The data suggest that microspheres may serve as a basic vaccine strategy for protection against HIV vaginal transmission. This renewal application develops microsphere-based vaccines and other strategies for protection against heterosexual transmission, using the following specific aims: Aim 1. To identify the best of three immunization strategies for induction of vaginal antibody and to determine which strategy is best for protection against vaginal SIV challenge. The three strategies are intramuscular (IM) immunization only, IM priming plus OR boosting and IM priming plus IT boosting. Aim 2. To test recombinant SIV formulations consisting of SIV expressed proteins in microspheres for induction of vaginal IgG and IgA levels that are comparable to our previous results with whole SIV-microsphere immunizations. We will also determine if these SIV-recombinant- microsphere immunized animals are protected against vaginal challenge. Aim 3. To produce concentrated vaginal SIV antibody for testing its functions in neutralization and other immunological assays. Aim 4. To compare the thigh and arm muscles as intramuscular immunization sites for priming the induction of SIV vaginal immunity. Aim 5. To conduct immunogenicity studies in macaques using HIV recombinant antigens for inducing vaginal and systemic immunity. Aim 6. To develop a reliable male genital SIV challenge system.