INTEGRATED AIDS VACCINE DEVELOPMENT PROGRAM

本次方案项目申报的主要目标是开展 背景下三种新候选疫苗的临床前研究 识别现有保护性疫苗中的保护性相关因素 模特。这些研究将为制定一项长期的 人类病毒学研究所(IHV)，新的候选疫苗将在其中 从受孕到人体试验。没有人体试验是 将描述在本申请中由一种方法提出的 候选疫苗将被带入这样的试验。此应用程序 代表着我们朝着这一目标迈出的第一步。因此，基金是 要求进行研究，其中候选疫苗将被提炼或 发展起来的。本项目由4个项目组成。项目1测试 假设对CD4-gp120复合体上的表位的体液反应 确定共受体结合可以预防原发感染 HIV-1。项目2探索一种新的抗原递送系统，该系统基于 减毒细菌毒素诱导第I类MHC限制性T细胞 回应。项目3建立在Out Group之前的工作基础上进行开发 评估新的基于沙门氏菌的HIV-1和SIV递送系统 抗原。这3个项目中的每一个都包括SHIV挑战研究，以 在动物模型中确定疫苗效力。这三个国家的一个主要目标 项目是确定至少一种新的候选疫苗进行携带 期待在支持期结束时进行人体试验。项目4 试图在交叉免疫的模型中定义保护性免疫的相关性 HIV-1抗原免疫恒河猴诱导的免疫保护作用 用HIV-2挑战他们。这个项目将检验这一假设 这种交叉保护是由病毒抑制因子(VSF)介导的 和/或由T细胞精心设计的抗病毒趋化因子。这样做的一个主要目标是 该项目的目的是确定可用于 设计针对人类免疫缺陷病毒的新疫苗。已被占用 这4个项目加在一起，应该会提供重要的新机会 用于开发安全有效的艾滋病毒-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.