USE OF THE SHIV AND SIV MODELS OF AIDS FOR HIV VACCINE DEVELOPMENT

使用艾滋病的 SHIV 和 SIV 模型开发 HIV 疫苗

• 批准号: 6299715
• 负责人: NORMAN L LETVIN
• 金额: $ 31.92万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6299715
• 关键词: AIDS vaccines; Macaca mulatta; cellular immunity; cytokine; cytotoxic T lymphocyte; helper T lymphocyte; human immunodeficiency virus 1; inhalation drug administration; leukocyte activation /transformation; mucosal immunity; polymerase chain reaction; recombinant virus; simian immunodeficiency virus; synthetic antigens; tissue /cell culture; vaccine development; virus antigen

Failures to date in our effort to create an effective AIDS vaccine can be explained, at least in part, by two shortcomings: (1) a lack of appreciation of the potential importance of virus-specific cell-mediated immunity in preventing HIV-1 infection, and (2) an inability to overcome the problem of viral diversity. Recent advances in our understanding of vaccine technologies that can elicit effector T cell responses and the development of important new non-human primate model systems for studying AIDS vaccine development make it possible now to begin addressing some of these issues in a meaningful way. We have shown now that peptides, live recombinant organisms and plasmid DNA can licit AIDS virus-specific CTL in higher primate species. We have also developed a chimeric virus expressing a primary patient HIV-1 envelope on an SIVmac backbone that can infect and induce AIDS in macaque species. These tools will be harnessed in the proposed studies to explore in rhesus monkeys: 1. HIV-1 envelope V3 loop peptide-elicited immunity 2. Vaccination to broaden CTL recognition of variant viruses 3. Cytokine profiles of CD4+ T cells following infections and vaccinations 4. Novel HIV vaccine strategies.

迄今为止，我们未能研制出有效的艾滋病疫苗，至少部分原因在于两个缺点：（1）对病毒特异性细胞介导的免疫在预防HIV-1感染中的潜在重要性缺乏认识，（2）无法克服病毒多样性的问题。最近我们对疫苗技术的理解取得了进展，可以引起效应T细胞反应，并开发了重要的新的非人灵长类动物模型系统，用于研究艾滋病疫苗的开发，使我们有可能开始以有意义的方式解决这些问题。我们现在已经证明，肽，活的重组生物体和质粒DNA可以在高等灵长类动物中激活艾滋病病毒特异性CTL。我们还开发了在SIVmac骨架上表达主要患者HIV-1包膜的嵌合病毒，其可以在猕猴物种中感染和诱导AIDS。这些工具将被利用在拟议的研究中，以探索恒河猴：1。HIV-1包膜V3环肽引起的免疫2.疫苗接种以扩大变异病毒的CTL识别3.感染和疫苗接种后CD 4 + T细胞的细胞因子谱4.新的艾滋病毒疫苗战略。