NOVEL RECOMBINANT ADENOVIRUS VACCINE VECTORS FOR HIV/SIV IN RHESUS MONKEYS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。开发HIV-1疫苗的一个关键障碍是我们目前无法有效地将HIV-1抗原传递到免疫系统，并启动人类可预测的高频免疫反应。例如，质粒DNA和重组痘病毒疫苗在表达抗原方面效率低下，到目前为止已被证明在人类身上的免疫原性很差。相比之下，基于重组腺病毒血清型5(RAd5)载体的疫苗在动物模型中表现出令人印象深刻的免疫原性，因此正在进入大规模临床试验。然而，发展中国家对Ad5载体预先存在的高频率免疫很可能会大大削弱针对HIV-1的rAd5疫苗的免疫原性和临床用途。为了克服这一障碍，我们正在开发基于稀有Ad血清型的新型复制不能复制的Rad载体疫苗。我们用表达SIV Gag和HIV-1 Env的rAd5、rAd35、嵌合rAd35k5和嵌合rAd5HVR48载体免疫恒河猴，以探讨这些候选疫苗的免疫原性。

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 critical roadblock in the development of an HIV-1 vaccine is our current inability to deliver HIV-1 antigens efficiently to the immune system and to prime predictable, high frequency immune responses in humans. For example, plasmid DNA and recombinant poxvirus vaccines are inefficient at expressing antigens and have proven poorly immunogenic in humans to date. In contrast, recombinant adenovirus serotype 5 (rAd5) vector-based vaccines have demonstrated impressive immunogenicity in animal models and are therefore being advanced into large-scale clinical trials. However, the high frequency of pre-existing immunity to the Ad5 vector in the developing world will likely substantially blunt the immunogenicity and clinical utility of rAd5 vaccines for HIV-1. To overcome this hurdle, we are developing novel replication-incompetent rAd vector-based vaccines derived from rare Ad serotypes. We immunized rhesus monkeys with rAd5, rAd35, chimeric rAd35k5, and chimeric rAd5HVR48 vectors expressing SIV Gag and HIV-1 Env to explore the immunogenicity of these candidate vaccines.