COMPARISON OF SIV DNA AND ATTENUATED VIRUS VACCINES

这笔赠款是作为综合计划下一揽子计划的一部分提交的 临床前/临床艾滋病疫苗开发计划[PAR-97-056]。这个 一揽子计划的主题是确定保护机制 用减毒的新城疫病毒免疫猴子。它已经被反复展示过了 感染减毒SIV可以保护猴子免受 致命的SIV病毒。然而，免疫反应的性质(S)是 对于保护的重要性仍未界定。虽然是实况衰减的 艾滋病疫苗可能永远不会足够安全，临床使用，了解 减毒病毒提供保护的机制将提供 在设计安全有效的艾滋病毒项目时使用的关键信息 将检验一种假设，即裸体免疫恒河猴 转录下整合SHIV89.6基因的DNA构建 对新启动子的控制可以保护动物免受阴道攻击 带着致命的SIV病毒。引诱病毒所需的最低病毒成分 通过增加对猴子的免疫可以确定保护措施 包含一个或多个SHIV89.6的复杂结构混合物 病毒基因，然后用毒力SIV挑战猴子。此外， 使用非慢病毒启动子来控制表达可能会减少 免疫和预防阴道感染之间的间隔时间 致命的SIV病毒。计划了三个具体目标：目标1)开发载体 并优化了核酸疫苗接种方法，用于两种疫苗的免疫 或更多的抗原基因，目的2)研究 DNA中的免疫刺激序列(ISS)在免疫反应中的作用 并确定它们是否可以用来增强免疫力 由质粒注射产生，目的3)以确定最小 猪瘟保护性核酸疫苗的抗原组成 SHIV89.6。Env基因单独诱导的免疫应答和保护作用 将与env和one或 更多其他病毒基因。此项目请求支持 制备上述列出的疫苗，并在#年进行初步测试 老鼠。灵长类动物免疫反应分析及面临的挑战 研究将利用项目1中的资源进行。

This grant is submitted as part of a package under the INTEGRATED PRECLINICAL/CLINICAL AIDS VACCINE DEVELOPMENT program [PAR-97-056]. The theme of the package is to determine the mechanism of protection in monkeys immunized with attenuated SHIV. It has been shown repeatedly that infection with attenuated SIV protects monkeys from challenge with virulent SIV. However the nature of the immune response(s) that are important for the protection remain undefined. Although live-attenuated HIV vaccines may never be safe enough for clinical use, understanding the mechanism by which attenuated viruses confer protection will provide critical information for use in designing safe and effective HIV Project will test the hypothesis that immunization of rhesus macaques with naked DNA constructs incorporating SHIV89.6 genes under the transcriptional control of novel promoters can protect animals from vaginal challenge with virulent SIV. The minimum viral components required for eliciting protection can be determined by immunizing monkeys with increasing complex mixtures of constructs which incorporate one or more SHIV89.6 viral genes, then challenging the monkeys with virulent SIV. Further, the use of non-lentiviral promoters to control expression may reduce the interval between immunization and protection from vaginal challenge with virulent SIV. Three specific aims are planned: Aim 1) Develop vectors and optimize nucleic acid vaccination methods for immunization with two or more antigen genes, Aim 2) Investigate the role that Immunostimulatory Sequences (ISS) in the DNA play in immune responses in primates and to determine if they can be used to enhance the immunity generated by the plasmid injections, Aim 3) To determine the minimal antigenic composition of a protective nucleic acid vaccine against SHIV89.6. Immune responses and protection induced by the env gene alone will be compared to those induced by a combination of env and one or more other viral genes. This project requests support for the preparation of the above listed vaccines and for initial testing in mice. The immune response analysis in primates and the challenge studies will be done using resources in Project 1.