INTEGRATED AIDS VACCINE DEVELOPMENT PROGRAM

本计划项目申请的主要目标是开展 三种新候选疫苗的临床前研究 在现有的保护性疫苗中， 模型这些研究将为长期计划提供基础， 人类病毒学研究所（IHV），新的候选疫苗将在 从受孕到人体试验没有人体试验 将描述在本申请中提出的一种方法， 候选疫苗将用于这些试验。本申请 代表着我们朝着这个目标迈出的第一步因此，资金 要求进行研究，其中候选疫苗将被完善，或 开发该项目包括4个项目。项目1测试 假设对CD 4-gp 120复合物上表位的体液应答， 确定辅助受体结合可以防止原发性感染 HIV-1项目2探索了一种新的抗原递送系统， 减毒细菌毒素以引发I类MHC限制性T细胞 应答项目3建立在我们小组以前的工作基础上， 并评估基于沙门氏菌的HIV-1和SIV新的传递系统 抗原这3个项目中的每一个都包括SHIV挑战研究， 确定疫苗在动物模型中的效力。这三个主要目标 项目的目的是确定至少一种新的候选疫苗， 在支持期结束前进行人体试验。项目4 试图在交叉免疫模型中定义保护性免疫的相关性， 用HIV-1抗原免疫恒河猴诱导的保护作用， 用HIV-2挑战他们。这个项目将测试假设， 这种交叉保护是由病毒抑制因子（VSF）介导的， 和/或由T细胞加工的抗病毒趋化因子。一个主要目标是 项目的目的是确定一个保护的相关性， 设计新的人类免疫缺陷病毒疫苗。采取 这四个项目将共同提供重要的新机会 开发安全有效的HIV-1疫苗。

The principal goal of this program project application is to carry out preclinical research on three new vaccine candidates against the backdrop of identifying correlates of protection in an existing protective vaccine model. These studies will provide the basis for a long-term program of the Institute of Human Virology (IHV) in which new vaccine candidates will be shepherded from conception through human trials. No human trials are proposed in this application by a process will be described whereby a candidate vaccine will be carried forward to such trials. This application represents our first step toward that goal. Accordingly, funds are requested for studies in which vaccine candidates will be refined or developed. This program consists of 4 projects. Project 1 tests the hypothesis that humoral responses to epitopes on a CD4-gp120 complex that determine co-receptor binding can protect against primary infection with HIV-1. Project 2 explores a new antigen delivery system that is based on attenuated bacterial toxins to elicit Class I MHC restricted T cell responses. Project 3 builds upon previous work from out group to develop and evaluate new Salmonella based delivery systems for HIV-1 and SIV antigens. Each of these 3 projects includes SHIV challenge studies to determine vaccine efficacy in an animal model. A major goal of these 3 projects is to identify at least one new vaccine candidate to carry forward to human trials by the end of the period of support. Project 4 seeks to define a correlate of protective immunity in a model of cross- protection induced by immunizing rhesus macaques with HIV-1 antigens and challenging them with HIV-2. This project will test the hypothesis that this cross protection is mediated by Virus Suppressive Factors (VSF) and/or anti-viral chemokines elaborated by T cells. A major goal of this project is to identify a correlate of protection that can be used to design new vaccines against human immunodeficiency viruses. Taken together, these 4 projects should provide significant new opportunities for the development of a safe and effective vaccine against HIV-1.