Manufacturing and Regulatory Support of Ad/MVA and Ad/Protein HIV-1 Vaccines

项目总结（见说明）： 项目3的目标是使Crucell装瓶、释放和管理表达HIV-1嵌合Env/Gag/Pol抗原和我们的稳定进化枝C HIV-1 Env gp 140三聚体的临床级Ad 26载体，用于项目2中描述的1期研究以及潜在的未来2a/2b期临床研究。 作为我们正在进行的IPCAVD A1078526计划的一部分，我们目前正在GMP条件下生产表达嵌合Env/Gag/Pol抗原以及我们的稳定进化枝C gp 140三聚体的多价Ad 26载体，用于临床试验。将生产足够的散装材料以支持I期和2a/2b期临床试验。然而，我们的IPCAVD AI 078526计划将于2013年结束，因此我们需要新的 IPCAVD拨款进一步开发这些新型HIV-1候选疫苗。 在本项目中，Crucell将灌装并放行剩余的Ad 26原料药和HIV-1 Env gp 140三聚体，以支持项目2中描述的I期研究和未来潜在的2a/2b期临床研究。Crucell还将提供该IPCAVD计划所需的所有监管和项目管理支持。为实现这些目标，我们提出以下三个具体目标： 1.在GMP条件下小瓶化、释放和监测表达HIV-1嵌合Env/Gag/Pol抗原的临床级Ad 26载体的稳定性; 2.在GMP条件下装瓶、释放和监测临床级HIV-1 Env gp 140三聚体的稳定性;和 3.提供本IPCAVD计划所需的法规和项目管理支持。

PROJECT SUMMARY (See instructions): The goal of Project 3 is for Crucell to vial, release, and manage clinical-grade Ad26 vectors expressing HlV-1 mosaic Env/Gag/Pol antigens and our stable clade C HlV-1 Env gp140 trimer for the phase 1 studies described in Project 2 as well as for potential future phase 2a/2b clinical studies. As part of our ongoing IPCAVD A1078526 program, we are currently manufacturing multivalent Ad26 vectors expressing mosaic Env/Gag/Pol antigens as well as our stable clade C gp140 trimer under GMP conditions for clinical trials. Sufficient bulk material will be manufactured to support both phase 1 and phase 2a/2b clinical trials. However, our IPCAVD AI078526 program will end in 2013, and thus we would require this new IPCAVD grant to develop these novel HlV-1 vaccine candidates further. In this project, Crucell will fill and release the remainder of the Ad26 drug substance and the HIV-1 Env gp140 trimer to support the phase 1 studies described in Project 2 and for potential future phase 2a/2b clinical studies. Crucell will also provide all the regulatory and project management support required for this IPCAVD program. To accomplish these goals, we propose the following three Specific Aims: 1. To vial, release, and monitor stability of clinical-grade Ad26 vectors expressing HlV-1 mosaic Env/Gag/Pol antigens under GMP conditions; 2. To vial, release, and monitor stability of clinical-grade HlV-1 Env gp140 trimer under GMP conditions; and 3. To provide the regulatory and project management support required for this IPCAVD program.