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预防候选疫苗， 载体平台，评估这些变化如何影响潜在所需的剂量和方案， 临床试验材料的生产以及表征和放行试验。早期过程 将对下一代HCMV/HIV载体候选物进行开发（PD）工作， 项目1-4确保下游制造成功。我们将在现有的和 新的细胞系，并优化目前的生产策略，目标是提高总产率（在 10倍），用于未来的生产。一旦适当的主干、插入和PD流程到位， 候选构建体准备就绪后，我们将生成所需的疫苗种子储备液（VSS）并生产主疫苗 细胞库（MCB）和工作细胞库（WCB）。我们将进行示范和工程运行， 确保GMP生产成功，并生成用于GLP毒理学研究的材料。我们将召开 与FDA召开IND前会议，以确保我们的放行试验、生产计划、详细的毒理学 研究和我们的1期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。年级 我们将进行一个广泛的第一阶段试验，部分基于数据，学习和问题。 在进行第一代疫苗HIV的安全性和免疫原性试验期间出现的 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.