MOLECULAR ADJUVANTS FOR MALT BASED IMMUNITY TO SIV/HIV

描述：该提案将探索细胞和分子机制 诱导对SIV和HIV特异性的粘膜和全身免疫应答 通过鼻相关淋巴网状组织（NALT）。 他们将 使用无毒霍乱毒素突变体作为佐剂与SIV组合 gp 130或HIV gp 160鼻内递送作为了解 在小鼠和人类中的诱导途径。 在另一项提案中，他们 旨在进行类似SIV/猕猴模型的研究。 在目标1中，申请人 将描述鼻给药后小鼠NALT和相关粘膜组织的特征 用SIV gp 130（或HIV gp 160）和mCT免疫，并在体外开发一种 人NALT系统来评估mCT诱导的抗原摄取。 在目标2，信号 将分析NALT抗原特异性CD 4 + T细胞的转导途径 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Th 1或Th 2型的诱导的嵌合mCT 鼻免疫后的反应。 在目标4中，他们将评估 mCTs对人扁桃体和腺样体抗原呈递细胞的作用 用于增强Th 1或Th 2型应答。 在目标5中，他们将 确定gp 160和mCT鼻用组合的安全性和免疫原性 在第一阶段的疫苗试验中，

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.