MUCOSAL AND SYSTEMIC IMMUNITY TO SIV AND HIV ANTIGENS

这项研究的总体目标是开发出能够预防 雄性和雌性猕猴通过生殖器传播SIV。保护 关于猕猴对抗静脉注射SIV攻击的研究一直在进行 成功，但人类艾滋病毒疫苗也必须防止 异性感染途径。在我们之前的NCVDG研究中，女性 猕猴被保护免受阴道的挑战。保护措施是 用福尔马林处理过的SIV免疫动物取得的成就 生物可降解微球，仅在肌肉内启动并由 经口(OR)或经气管(IT)途径。或者，仅靠免疫并不能 保护好自己。数据表明，微球可能是一种基本疫苗。 预防艾滋病毒经阴道传播的战略。此次续订 应用程序开发基于微球的疫苗和其他策略 针对异性传播的保护，使用以下具体措施 目标： 目标1.确定三种免疫策略中最佳的一种 诱导阴道抗体，并确定哪种策略最适合 对阴道SIV挑战的保护。这三种策略是 仅肌肉(IM)免疫、IM启动加或增强和IM 引爆加上IT助推器。 目的2.检测由SIV表达的重组SIV制剂 微球中的蛋白质可诱导阴道免疫球蛋白和免疫球蛋白A水平 与我们之前用整个SIV微球得到的结果相当 免疫接种。我们还将确定这些SIV重组- 微球免疫的动物受到保护，免受阴道攻击。 目的3.制备用于检测SIV的浓缩阴道SIV抗体 在中和和其他免疫学检测中起作用。 目的4.比较大腿肌肉和手臂肌肉作为肌肉免疫的作用 SIV阴道免疫诱导的启动部位。 目的5.利用HIV对猕猴进行免疫原性研究 用于诱导阴道和全身免疫的重组抗原。 目的6.建立可靠的男性生殖器SIV攻击系统。

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.