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

用于预防性 HIV/AIDS 疫苗的安全性和有效性优化的第二代 HCMV/HIV 载体的临床开发

• 批准号: 9239374
• 负责人: Thomas G Evans
• 金额: $ 15.2万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9239374
• 关键词: Affect; Back; Biological Assay; CD8-Positive T-Lymphocytes; Cell Line; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Clinical trial protocol document; Contracts; Cytomegalovirus; Data; Development; Development Plans; Dose; Engineering; Ensure; Epitopes; Fibroblasts; Frequencies; Funding; Future; Gene Expression; Generations; Genes; Genetic; Goals; Growth; HIV; HIV vaccine; Immune; Intercept; Learning; Macaca mulatta; Maintenance; Major Histocompatibility Complex; Manufactured Materials; Mediating; Modeling; Modification; Molecular; Mosaicism; Nature; Pathogenicity; Phase; Phase I Clinical Trials; Procedures; Process; Production; Regimen; Reporting; Running; SIV; Safety; Seeds; Site; T cell response; T memory cell; Testing; Tissues; Toxicity Tests; Toxicology; Vaccinated; Vaccination; Vaccines; Vertebral column; Viral; Virus; Virus Diseases; Work; assay development; attenuation; base; cell bank; clinical development; design and construction; immunogenicity; manufacturing process; meetings; next generation; novel; phase I trial; pre-clinical; product development; programs; prophylactic; prototype; repaired; response; success; vaccine candidate; vector

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.

项目5总结 OHSU 团队基于 HCMV 开发下一代 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、 临床试验材料的制造以及表征和释放测定。早期流程 开发（PD）工作将针对由以下公司生产的下一代 HCMV/HIV 候选载体进行： 项目 1-4 确保下游制造成功。我们将确定现有和 新的细胞系并优化当前的制造策略，目标是提高总体产量（在 至少10倍）用于未来的生产。一旦适当的主干、插入和 PD 流程就位并 候选构建准备就绪，我们将生成所需的疫苗种子库存 (VSS) 并生成母版 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 生产成功并为 GLP 毒理学研究生成材料。我们将举办 与 FDA 举行 IND 前会议，以确保我们的释放分析、生产计划、详细毒理学 研究和我们的一期临床概要都是可以接受的。这项工作将完成并提供 GMP 材料， 毒理学报告和临床试验方案在第 4 年年底准备好，以提交所需的 IND。当年 在该计划的第 5 部分中，我们将部分基于数据、经验教训和问题进行广泛的第一阶段试验 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问题 候选疫苗。