COMPARISON OF SIV DNA AND ATTENUATED VIRUS VACCINES

SIV DNA 和减毒病毒疫苗的比较

• 批准号: 6511096
• 负责人: GARY H RHODES
• 金额: $ 23万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6511096
• 关键词: Macaca mulatta; active immunization; attenuated microorganism; immunologic assay /test; laboratory mouse; plasmids; simian immunodeficiency virus; vaccine development; vector vaccine; viral vaccines; virulence; virus DNA; virus antigen; virus envelope; virus genetics

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.

这笔赠款作为综合计划下的一揽子计划的一部分提交 临床前/临床艾滋病疫苗开发计划 [PAR-97-056]。 这 该软件包的主题是确定保护机制 猴子接种了减毒 SHIV 疫苗。 已经被反复展示过 减毒 SIV 感染可以保护猴子免受 剧毒的SIV。然而，免疫反应的性质是 对于保护的重要性仍未定义。 虽然现场衰减 HIV 疫苗对于临床使用可能永远不够安全，理解 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 将检验用裸露疫苗对恒河猴进行免疫的假设 在转录下整合 SHIV89.6 基因的 DNA 构建体 控制新型启动子可以保护动物免受阴道攻击 带有剧毒的SIV。 引发所需的最低病毒成分 可以通过对猴子进行免疫接种来确定保护作用 包含一种或多种 SHIV89.6 的复杂构建体混合物 病毒基因，然后用剧毒的 SIV 攻击猴子。 更远， 使用非慢病毒启动子来控制表达可能会减少 免疫接种和预防阴道感染之间的间隔 剧毒的SIV。 计划了三个具体目标： 目标 1) 开发载体 优化核酸疫苗接种方法，进行两种免疫 或更多抗原基因，目标 2) 研究 DNA 中的免疫刺激序列 (ISS) 在免疫反应中发挥作用 在灵长类动物中，并确定它们是否可以用于增强免疫力 由质粒注射产生，目标 3) 确定最小 一种保护性核酸疫苗的抗原组合物 SHIV89.6。 env 基因单独诱导的免疫反应和保护 将与由 env 和一个或一个的组合诱导的那些进行比较 更多其他病毒基因。 该项目请求支持 制备上述疫苗并进行初步测试 老鼠。 灵长类动物的免疫反应分析和挑战 研究将使用项目 1 中的资源进行。

项目成果

Protection against challenge with measles virus (MV) in infant macaques by an MV DNA vaccine administered in the presence of neutralizing antibody.

在中和抗体存在的情况下注射 MV DNA 疫苗，可保护幼年猕猴免受麻疹病毒 (MV) 的攻击。

• DOI: 10.1086/420792
• 发表时间: 2004
• 期刊: The Journal of infectious diseases
• 作者: Premenko-Lanier,Mary;Rota,PaulA;Rhodes,GaryH;Bellini,WilliamJ;McChesney,MichaelB
• 通讯作者: McChesney,MichaelB

Prior DNA vaccination does not interfere with the live-attenuated measles vaccine.

先前的 DNA 疫苗接种不会干扰麻疹减毒活疫苗。

• DOI: 10.1016/j.vaccine.2003.08.020
• 发表时间: 2004
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Premenko-Lanier,Mary;Rota,Paul;Rhodes,Gary;Bellini,William;McChesney,Michael
• 通讯作者: McChesney,Michael