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: 6099763
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6099763
• 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，我们在研制有效艾滋病疫苗方面的失败至少可以部分地归因于两个缺点：(1) 缺乏对病毒特异性细胞介导的免疫在预防 HIV-1 感染方面的潜在重要性的认识，以及 (2) 无法克服病毒多样性的问题。我们对能够引发效应 T 细胞反应的疫苗技术的理解的最新进展，以及用于研究艾滋病疫苗开发的重要的新型非人类灵长类动物模型系统的开发，使得现在有可能开始以有意义的方式解决其中一些问题。我们现在已经证明，肽、活重组生物和质粒 DNA 可以在高等灵长类动物中引发艾滋病病毒特异性 CTL。我们还开发了一种在 SIVmac 骨架上表达原发性患者 HIV-1 包膜的嵌合病毒，该病毒可以在猕猴物种中感染并诱发艾滋病。这些工具将在拟议的研究中利用，在恒河猴中进行探索： 1. HIV-1 包膜 V3 环肽引发的免疫 2. 疫苗接种以扩大 CTL 对变异病毒的识别 3. 感染和疫苗接种后 CD4+ T 细胞的细胞因子谱 4. 新型 HIV 疫苗策略。