MOLECULAR ADJUVANTS FOR MALT BASED IMMUNITY TO SIV/HIV

描述：该计划将探索细胞和分子机制。 诱导针对SIV和HIV的粘膜和系统免疫反应 通过鼻腔相关淋巴网状组织(NALT)。他们会 使用无毒霍乱毒素突变体作为佐剂与SIV结合 Gp130或HIV gp160鼻腔注射作为一种了解 小鼠和人类的诱导途径。在另一项提案中，他们 目的对SIV/猕猴模型进行类似的研究。在目标1中，申请人 将表征小鼠NALT和相关的鼻腔粘膜组织 SIV gp130(或HIV gp160)与MCT免疫并建立体外 人NALT系统评估MCT诱导的抗原摄取。在目标2中，信号 将分析NALT抗原特异性CD4+T细胞的转导途径 在鼻腔免疫后。在目标3中，他们将开发和描述 可模拟抗原特异性Th1或Th2型诱导的嵌合MCT 鼻腔免疫后的反应。在目标4中，他们将评估 巨噬细胞集落刺激因子对人扁桃体和腺样体抗原提呈细胞的影响 用于增强Th1或Th2型反应。在《目标5》中，他们将 联合应用gp160和MCT鼻腔疫苗的安全性和免疫原性研究 第一阶段疫苗试验中的人体疫苗。

DESCRIPTION: This proposal will explore cellular and molecular mechanisms to induce mucosal and systemic immune responses specific for SIV and HIV through the nasal-associated lymphoreticular tissue (NALT). They will employ non-toxic cholera-toxin mutants as adjuvants in combination with SIV gp130 or HIV gp160 delivered intranasally as a means to understand the induction pathways in both mice and humans. In a separate proposal, they aim to conduct similar studies SIV/macaque model. In Aim 1, the applicant will characterize murine NALT and associated mucosal tissues after nasal immunization with SIV gp130 (or HIV gp160) with mCT and develop an in vitro human NALT system to assess mCT-induced antigen uptake. In Aim 2, signal transduction pathways of NALT antigen-specific CD4+ T cells will be analyzed following nasal immunization. In Aim 3, they will develop and characterize chimeric mCTs which can mimic induction of antigen-specific Th1 or Th2 type responses following nasal immunization. In Aim 4, they will assess the effects of mCTs on antigen-presenting cells from human tonsils and adenoids for potentiation of Th1-or Th2-type responses. In Aim 5, they will determine the safety and immunogenicity of a combined gp160 and mCT nasal vaccine in humans in a phase I vaccine trial.