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

用于恒河猴 HIV/SIV 的新型重组腺病毒疫苗载体

• 批准号: 7349540
• 负责人: Dan H. Barouch
• 金额: $ 13.48万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349540
• 关键词: NOVEL; RECOMBINANT; ADENOVIRUS; VACCINE; VECTORS

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.

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。开发HIV-1疫苗的一个关键障碍是，我们目前无法将HIV-1抗原有效地递送到免疫系统，并在人体中引发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，迄今已证明在人类中免疫原性较差。相比之下，重组腺病毒血清型5 （rAd5）载体疫苗在动物模型中显示出令人印象深刻的免疫原性，因此正在推进大规模临床试验。然而，发展中国家对Ad5载体的高频率预先免疫可能会大大削弱针对HIV-1的rAd5疫苗的免疫原性和临床应用。为了克服这一障碍，我们正在开发从罕见Ad血清型中提取的新型无复制能力的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，探讨这些候选疫苗的免疫原性。