INDUCTION OF MUCOSAL IMMUNITY TO HIV IMMUNOGENS

HIV免疫原诱导粘膜免疫

• 批准号: 6268149
• 负责人: Thomas J. Palker
• 金额: $ 12.43万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6268149
• 关键词: AIDS vaccines; HIV envelope protein gp120; HIV infections; Macaca fascicularis; chimeric proteins; cholera toxin; complement; cooperative study; cytotoxic T lymphocyte; disease /disorder model; genital secretion; human immunodeficiency virus 1; human subject; immunoglobulin A; immunoglobulin G; laboratory mouse; laboratory rabbit; microcapsule; mucosal immunity; neutralizing antibody; secretion; serum; synthetic peptide; virus antigen

The overall goal of this project is to develop mucosally targeted subunit vaccines that can elicit potent mucosal and systemic neutralizing antibodies and major histocompatibility compels (MHC) class I restricted cytotoxic T-lymphocyte (CTL) responses to human immunodeficiency virus type 1 (HIV-1) and HIV-1 infected cells. Specific aims are as follows: Specific Aim 1. We will test the chimeric HIV peptide T1-SP10MN(A) administered to the mucosal surface of rabbits via chronically isolated ileal loops (Thiry-Vella model) for induction of HIV-neutralizing secretary IgA (S-IgA) and IgG in vaginal and gastrointestinal secretions and in serum. Specific Aim 2. We will incorporate mucosal adjuvants and the HIV peptide T1-SP10MN (A) into biodegradable poly (DL-lactide-co-glycoside) (DL-PLG) microsphere, administer these parenterally and orally to Balb/mice, and evaluate mucosal anti-HIV-1 S-IgA, IgG and MHC class I- restricted CTL responses. Specific Aim 3. We will characterized the mucosal immune response to parental immunization with the T1-Sp10MN (A) peptide in normal subjects. Specific Aim 4. We will assess in rhesus monkeys a peptide/adjuvant/microsphere inoculum designed to optimize an anti-HIV envelope mucosal immune response. Specific Aim 5. To study the ability of IgA to neutralize HIV-1, we will produce IgA monoclonal antibodies to the V3 domain of HIV-1 MN gp120 and measure their ability to neutralize HIV-1 and enhance HIV-1 infection in the presence and absence of complement.

该项目的总体目标是开发具有粘性的亚基 可以引起有效粘膜和全身中和的疫苗 抗体和主要的组织相容性强迫（MHC）I类限制 细胞毒性T淋巴细胞（CTL）对人免疫缺陷病毒的反应 1型（HIV-1）和HIV-1感染细胞。 具体目的如下： 具体目标1。我们将测试嵌合HIV肽T1-SP10MN（A） 通过长期分离到兔子的粘膜表面 回肠环（Thiry-Vella模型）用于诱导HIV中和 秘书IgA（S-IGA）和IgG在阴道和胃肠道分泌物中 和血清。 特定目标2。我们将融合粘膜佐剂和艾滋病毒 肽T1-SP10MN（A）进入可生物降解的聚（DL-丙二醇 - 糖苷） （dl-plg）微球，以肠胃外和口服给药 BALB/MICE，并评估粘膜抗HIV-1 S-IgA，IgG和MHC I类 受限的CTL响应。 特定目标3。我们将表征粘膜免疫反应 正常受试者中用T1-SP10MN（A）肽的父母免疫。 特定目标4。我们将在恒河猴中评估 肽/辅助/微球接种物，旨在优化抗HIV 包膜粘膜免疫反应。 具体目标5。研究IgA中和HIV-1的能力，我们将 对HIV-1 MN GP120和 衡量他们中和HIV-1并增强HIV-1感染的能力 没有补充的存在和不存在。