DEVELOPMENT OF EFFECTIVE HIV VACCINE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。设计全球HIV-1疫苗的一个主要障碍是病毒多样性。病原体的多样性并不是HIV-1所独有的，在其他领域，通过研制混合疫苗已经成功地克服了这种多样性。在这里，我们描述了HIV-1包膜鸡尾酒疫苗的测试。6只猕猴接种了重组DNA、重组痘苗病毒和重组包膜蛋白的连续免疫疫苗。接种疫苗后，动物对疫苗序列中没有的蛋白质和病毒产生了多种抗包膜抗体结合和中和活性。t细胞也被诱导，通过包膜衍生肽池的γ -干扰素产生试验来测量。接种疫苗的动物和对照动物分别用89.6P的异源致病性SHIV攻毒。与未接种疫苗的对照组相比，接种疫苗的猴子的病毒滴度明显降低，CD4+ t细胞的维持也更好。免疫组的B细胞和t细胞免疫反应在攻击后远优于接种组。6只接种疫苗的动物中有4只存活了44周的观察期，6只对照动物中只有1只存活了下来。本报告首次描述了由一种不含89.6或SIV衍生物的异源HIV-1疫苗介导的致病性SHIV疾病控制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A central obstacle to the design of a global HIV-1 vaccine is virus diversity. Pathogen diversity is not unique to HIV-1, and has been successfully conquered in other fields by the creation of vaccine cocktails. Here we describe the testing of an HIV-1 envelope cocktail vaccine. Six macaques received the vaccine, delivered by successive immunizations with recombinant DNA, recombinant vaccinia virus and recombinant envelope proteins. Following vaccination, animals developed a diversity of anti-envelope antibody binding and neutralizing activities toward proteins and viruses that were not represented by sequence in the vaccine. T-cells were also elicited, as measured by gamma-interferon production assays with envelope-derived peptide pools. Vaccinated and control animals were then challenged with the heterologous pathogenic SHIV, 89.6P. Vaccinated monkeys experienced significantly lower virus titers and better maintenance of CD4+ T-cells than unvaccinated controls. The B- and T-cell immune responses were far superior post-challenge in the vaccinated group. Four of six vaccinated animals and only one of six control animals survived a 44-week observation period post-challenge. The present report is the first to describe pathogenic SHIV disease control mediated by a heterologous HIV-1 vaccine, devoid of 89.6 or SIV derivatives.