PROTECTIVE IMMUNITY TO HUMAN IMMUNODEFICIENCY VIRUS

对人类免疫缺陷病毒的保护性免疫力

基本信息

批准号：
3547126
负责人：
EDWARD S. Edward S Mocarski
金额：
$ 22.78万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-03-01 至 1991-02-28
项目状态：
已结题

项目摘要

This application is in response to RFA-NIH-NIAID-87-AI-21, a request for National Cooperative Vaccine Development Groups for the Acquired Immunodeficiency Syndrome (AIDS). We have brought together a critical mass of four scientists within Stanford Medical Center with past interactions who each propose individual efforts aimed at HIV vaccination. The projects will systematically examine neutralizing epitopes on HIV and express HIV antigens in prokaryotic and eukaryotic expression vectors, and constitute creative approaches to all of the goals set out in the RFA: (i) whole HIV vaccine, (ii) subunit vaccine, (iii) recombinant DNA produced antigens, (iv) synthetic vaccines, and (v) use of viral vectors. Project I (Dr. Harry Greenberg) will isolate HIV neutralizing monoclonal antibodies, use these antibodies to define neutralizing epitopes and devise neutralizing epitope specific blocking ELISAs to define the neutralizing antibody response in humans and animals. Project II (Dr. William Robinson) will utilize synthetic peptides to define protective epitopes on HIV proteins and use them in prokaryotic expression systems. Project III (Dr. Bruce Stocker) will introduce protective HIV epitopes into salmonella vaccine strains fused to flagellar or other bacterial proteins and test these in animals as a live attenuated recombinant bacterial vaccine vector. Project IV (Dr. Edward Mocarski) will introduce HIV protein and particulate (defective virus) antigens into cytomegalovirus expression vectors to produce high levels of protein in mammalian cells and to test recombinant CMV as a live virus vaccine vector in animals. The overall goals of the Program Project will be accomplished by the integration of information from these four projects, with the monoclonal antibody and synthetic peptide work together providing critical understanding of HIV neutralizing epitopes, with prokaryotic and eukaryotic vaccine vectors systems providing useful and practical approaches towards vaccination of humans and with assays that will enable quantitation of the neutralizing immune response in animals or humans without the need for inectious HIV. The work proposed describes new approaches and strategies for HIV vaccine development entirely of a preclinical nature, relying on the ability to raise HIV neutralizing antibody or induce a cellular response in vaccinated animals as indicators of protective immunity. In the future, vaccines developed through this Program Project will be readily tested in humans.

此应用是响应RFA-NIH-NIAID-87-AI-21，a 请求国家合作疫苗开发小组对于获得的免疫缺陷综合征（AIDS）。我们有将斯坦福大学的四名科学家汇集在一起每个人都建议个人的医疗中心旨在HIV疫苗接种的努力。项目将系统地检查艾滋病毒和表达的中和表位原核和真核表达载体中的HIV抗原，并构成了针对所有目标的创造性方法 RFA：（i）整个HIV疫苗，（ii）亚基疫苗，（iii）重组DNA产生抗原，（IV）合成疫苗，和（v）使用病毒载体。项目I（Harry Greenberg博士）将分离艾滋病毒中和单克隆抗体，使用这些定义中和表位并设计中和的抗体表位特异性阻止ELISA以定义中和人和动物的抗体反应。第二个项目（威廉博士罗宾逊）将利用合成肽来定义保护性艾滋病毒蛋白的表位并将其用于核表达系统。 III项目（Bruce Stocker博士）将引入保护性艾滋病毒表位成融合鞭毛或其他细菌蛋白质，并将其作为活物测试减弱的重组细菌疫苗载体。第四项目（博士 Edward Mocarski）将引入HIV蛋白和颗粒物（有缺陷的病毒）抗原进入巨细胞病毒表达载体在哺乳动物细胞中产生高水平的蛋白质并测试重组CMV作为动物中的活病毒疫苗载体。这该计划项目的总体目标将由从这四个项目中的信息集成，单克隆抗体和合成肽一起起作用提供对艾滋病毒中和表位的批判性理解，原核和真核疫苗载体系统提供有用且实用的人类疫苗接种方法并通过可以定量中和的测定动物或人类的免疫反应无需艾滋病毒。拟议的工作描述了新方法，艾滋病毒疫苗的策略完全是临床前的大自然，依靠提高艾滋病毒中和抗体的能力或诱导接种动物的细胞反应作为指标保护性免疫。将来，疫苗通过该计划项目将很容易在人类中进行测试。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse.

小鼠潜伏感染不需要单纯疱疹病毒潜伏 RNA (LAT)。

DOI：
10.1073/pnas.86.19.7596
发表时间：
1989
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Ho,DY;Mocarski,ES
通讯作者：
Mocarski,ES

Herpes simplex virus latency: molecular aspects.

单纯疱疹病毒潜伏期：分子方面。