MUCOSAL AND SYSTEMIC IMMUNITY TO SIV AND HIV ANTIGENS

对 SIV 和 HIV 抗原的粘膜和系统免疫

• 批准号: 5205375
• 负责人: PRESTON A MARX
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5205375
• 关键词: Macaca mulatta; human immunodeficiency virus; immunity; immunization; immunoglobulin A; immunoglobulin G; mucosa; mucosal immunity; neutralizing antibody; recombinant DNA; simian immunodeficiency virus; virus antigen

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.

这项研究的总体目标是开发可以保护的疫苗 来自生殖器SIV传播的男性和女性猕猴。 保护 针对SIV静脉注射挑战的猕猴的研究已经 成功，但是人类的艾滋病毒疫苗也必须预防 异性恋感染途径。 在我们以前的NCVDG研究中，女性 猕猴受到了阴道挑战的保护。 保护是 当动物在福尔马林处理的SIV中免疫时实现 仅当肌肉内引发并通过 口服（或）或气管内（IT）路线。 或仅免疫不 保护。 数据表明微球可以用作基本疫苗 防止艾滋病毒阴道传播的策略。 这个更新 应用开发基于微球的疫苗和其他策略 使用以下特定的特异性保护异性传播 目标： 目的1。确定三种免疫策略的最佳 诱导阴道抗体，并确定哪种策略最适合 防止阴道SIV挑战。 这三个策略是 仅肌肉内（IM）免疫，IM启动加或增强和IM 启动加上启动。 目标2。测试由SIV表示的重组SIV配方 微球中的蛋白质用于诱导阴道IgG和IgA水平 与我们先前的整个SIV微粒圈相当 免疫接种。 我们还将确定这些SIV重组是否是否 微球免疫动物受到阴道挑战的保护。 目标3。生产浓缩的阴道SIV抗体来测试其 中和和其他免疫学测定中的功能。 目标4。将大腿和手臂肌肉作为肌内免疫 启动SIV阴道免疫的部位。 目的5。使用HIV进行猕猴中的免疫原性研究 重组抗原，用于诱导阴道和全身免疫。 目标6。开发可靠的男性生殖器SIV挑战系统。