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

项目5总结

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.