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

项目总结(见说明)： 项目3的目标是让Crucell包装、释放和管理表达HLV-1马赛克Env/Gag/Pol抗原和我们稳定的C分支HLV-1 Env gp140三聚体的临床级AD26载体，用于项目2中描述的第一阶段研究以及潜在的未来2a/2b阶段临床研究。 作为我们正在进行的IPCAVD A1078526计划的一部分，我们目前正在生产表达马赛克Env/GAG/POL抗原的多价AD26载体以及我们在GMP条件下稳定的C gp140三聚体，用于临床试验。将生产足够的散装材料，以支持1期和2a/2b期临床试验。然而，我们的IPCAVD AI078526计划将于2013年结束，因此我们需要此新的 IPCAVD拨款进一步开发这些新型HLV-1候选疫苗。 在该项目中，Crucell将填充和释放AD26药物物质和HIV-1 Env gp140三聚体的剩余部分，以支持项目2中描述的第一阶段研究以及未来潜在的2a/2b阶段临床研究。CRUCEL还将提供IPCAVD项目所需的所有监管和项目管理支持。为了实现这些目标，我们提出了以下三个具体目标： 1.将表达HLV-1嵌合型Env/Gag/Pol抗原的临床级AD26载体包装、释放并监测其在GMP条件下的稳定性； 2.试瓶、释放和监测临床级HLV-1Env gp140三聚体在GMP条件下的稳定性；以及 3.提供IPCAVD计划所需的监管和项目管理支持。

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.