Development Of A Multicomponent HIV-1 Recombinant Adenoviral Vector Vaccine

本项目旨在制备GMP质量的研究性HIV疫苗，并完成多组分HIV-1腺病毒载体疫苗临床研究所需的临床前和实验室研究。假设疫苗对人类施用是安全的，并引起对HIV-1的免疫应答。受试者接受腺病毒载体疫苗作为单一药剂或在用质粒DNA疫苗引发后作为加强剂。NIAID疫苗研究中心（VRC）正在开发一种针对三种全球最流行的HIV亚型（进化枝）的新型初免-加强HIV疫苗策略。VRC的HIV初免-加强候选物旨在引发对来自进化枝A、B和C的HIV序列的免疫反应，这些进化枝共同导致全球约90%的HIV感染事件。2004年11月，VRC临床试验中心在NIH临床中心（Bethesda，MD）启动了多分支、多基因重组腺病毒载体5疫苗的I期临床研究（VRC 006），作为开发初免-加强方案的第一步。此后，该产品已在美国和国际研究中心的多项1期和2期临床试验中作为单药和DNA初免-腺病毒载体加强方案的一部分进行了临床评估。第二阶段材料的生产已经完成。

This project is designed to prepare a GMP quality investigational HIV vaccine and complete the preclinical and laboratory studies needed for clinical studies of a multicomponent HIV-1 adenoviral vector vaccine. The hypothesis is that the vaccine will be safe for human administration and elicit immune responses to HIV-1. Subjects receive adenovector vaccine either as a single agent or as a boost after priming with plasmid DNA vaccines. The Vaccine Research Center (VRC), NIAID is developing a novel prime-boost HIV vaccine strategy directed at the three most globally prevalent HIV subtypes (clades). VRC's HIV prime-boost candidate is designed to elicit immune responses to HIV sequences from clades A, B and C which together cause about 90 percent of incident HIV infections around the world. In November 2004, the VRC Clinical Trials Core launched a Phase I clinical study (VRC 006) of a multiclade, multigene recombinant adenovector 5 vaccine at the NIH Clinical Center (Bethesda, MD) as the first step in developing the prime-boost regimen. This product has since been evaluated clinically as a single agent and as part of a DNA prime-adenovector boost regimen in several Phase 1 and 2 clinical trials in U.S. and international sites. Production of Phase II materials has been completed.