COMPARISON OF SIV DNA AND ATTENUATED VIRUS VACCINES

该补助金是作为综合方案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项目[PAR-97-056]。 的 一揽子计划的主题是确定保护机制， 用减毒SHIV免疫的猴子。 它已经多次被证明 感染减毒SIV可以保护猴子免受 致命的SIV然而，免疫应答的性质是 重要的保护仍然没有定义。 虽然活减毒 艾滋病毒疫苗可能永远不足以安全用于临床使用，了解 减毒病毒提供保护的机制将提供 用于设计安全有效的艾滋病毒项目的关键信息 将测试这一假设，即免疫恒河猴与裸 在转录调控下掺入SHIV 89.6基因的DNA构建体 控制新的启动子可以保护动物免受阴道攻击 致命的SIV 引发病毒所需的最低病毒成分 保护作用可以通过用增加的免疫力免疫猴子来确定。 掺入一种或多种SHIV的构建体的复杂混合物89.6 病毒基因，然后用致命的SIV挑战猴子。 此外，本发明还 使用非慢病毒启动子来控制表达可以减少 免疫接种和保护免受阴道攻击之间的间隔， 致命的SIV 计划实现三个具体目标： 优化核酸疫苗接种方法， 或多个抗原基因，目的2）研究 DNA中的免疫刺激序列（ISS）在免疫应答中的作用 并确定它们是否可以用来增强免疫力 目的3）为了确定质粒注射产生的最小 一种抗病毒的保护性核酸疫苗的抗原组合物 SHIV89.6 单独env基因诱导的免疫应答和保护作用 将与由env和一种或多种药物的组合诱导的那些进行比较。 更多的病毒基因 该项目要求支持 上述疫苗的制备和初步试验 小鼠 灵长类动物免疫应答分析及攻毒 将利用项目1中的资源进行研究。

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.