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

迄今为止，我们未能创造出有效的艾滋病疫苗，这至少可以部分归因于两个缺陷：(1)缺乏对病毒特异性细胞免疫在预防艾滋病毒-1感染方面的潜在重要性的认识；(2)无法克服病毒多样性的问题。最近我们对疫苗技术的了解取得了进展，可以激发效应者T细胞反应，并开发了用于研究艾滋病疫苗开发的重要的非人类灵长类动物模型系统，这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，多肽、活的重组生物和质粒DNA可以在高等灵长类物种中合法地识别艾滋病病毒特异性的CTL。我们还开发了一种嵌合病毒，它在SIVmac主干上表达原发患者的HIV-1包膜，可以在猕猴物种中感染和诱导艾滋病。这些工具将在拟议的研究中用于在恒河猴身上探索：1.HIV-1包膜V3环肽诱导的免疫2.疫苗接种以扩大对变异病毒的CTL识别3.感染和接种后CD4+T细胞的细胞因子谱4.新的HIV疫苗策略。

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.