Clinical Development of a Safety and Efficacy-Optimized 2nd Generation HCMV/HIV Vector for a Prophylactic HIV/AIDS Vaccine

项目5摘要 随着OHSU团队开发基于HCMV的下一代HIV预防性候选疫苗 在载体平台上，评估这些变化如何影响潜在的所需剂量和方案将是至关重要的 临床试验材料的制作、表征和释药分析。早期流程 将对由以下公司生产的下一代HCMV/HIV候选载体进行开发(PD)工作 项目1-4以确保下游制造成功。我们将确定现有和 新的细胞系和优化现有的制造策略，目标是提高整体产量(在 至少10倍)，用于未来的生产。一旦适当的主干、插入和PD流程到位， 候选构建准备好了，我们将生成所需的疫苗种子库(VSS)并产生一个母体 细胞库(MCB)和工作细胞库(WCB)。我们将进行示范和工程运行，以 确保GMP生产成功，并为GLP毒理学研究提供材料。我们将举行一场 IND前与FDA的会议，以确保我们的释放化验，生产计划，详细的毒理学 研究和我们的第一阶段临床概要都是可以接受的。这项工作将完成，GMP材料， 毒理学报告和临床试验方案在第4年年底前准备好，以提交所需的IND。以年计 在该计划的5个阶段，我们将进行广泛的第一阶段试验，部分基于数据、学习和问题 在进行第一代艾滋病毒疫苗的安全性和免疫原性试验期间出现的问题 候选疫苗。

Project 5 Summary As the OHSU team develops the next generation HIV prophylactic candidate vaccines based on the HCMV vector platform, it will be critical to assess how the changes affect the potential needed dose and regimen, the manufacturing of the clinical trial materials, and the characterization and release assays. Early process development (PD) work will be performed on the next generation HCMV/HIV vector candidates produced by Projects 1-4 to ensure downstream manufacturing success. We will determine HCMV growth in existing and novel cell lines and optimize the present manufacturing strategies, with the goal to increase the overall yield (at least 10-fold) for future production. Once the appropriate backbone, insert, and PD processes are in place and the candidate constructs ready, we will generate the needed Vaccine Seed Stock (VSS) and produce a Master Cell Bank (MCB) and Working Cell Bank (WCB). We will undertake demonstration and engineering runs to ensure GMP manufacturing success and to generate material for the GLP toxicology studies. We will hold a pre-IND meeting with the FDA to ensure that our release assays, manufacturing plan, detailed toxicology studies, and our Phase 1 clinical synopsis are all acceptable. This work will be finished and the GMP material, toxicology report, and Clinical Trial Protocol ready by the end of year 4 for the required IND submission. In year 5 of the program we will conduct an extensive Phase 1 trial, based in part on the data, learnings, and issues that have arisen during the conduct of the safety and immunogenicity trial of the first generation vaccine HIV candidate vaccine.