Manufacturing of Novel Adenovirus Prime-Boost HIV-1 Vaccine

新型腺病毒 Prime-Boost HIV-1 疫苗的制造

• 批准号: 7906913
• 负责人: JAAP GOUDSMIT
• 金额: $ 1084.22万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 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/7906913
• 关键词: Adenoviruses; Adherence; Biological Assay; Biotechnology; Cell Line; Clinical; Clinical Research; Clinical Trials; Communicable Diseases; Development; Ensure; FDA approved; Gagging; Goals; HIV; HIV-1; HIV-1 vaccine; Harvest; Human; Malaria; Methods; Monitor; Oryctolagus cuniculus; Pharmacologic Substance; Phase; Population; Practice Guidelines; Procedures; Process; Production; Quality Control; Research; Seeds; Seroprevalences; Serotyping; South Africa; Toxicology; Translations; Tuberculosis; United States; Vaccines; Virus; authority; base; env Gene Products; improved; manufacturing process; novel; pathogen; pre-clinical; programs; quality assurance; vaccine candidate; vaccine development; vector; vector-based vaccine

The goal of this project is for Crucell to manufacture clinical-grade master virus seed stocks and trivalent, clinical-grade rAd26 and rAd5HVR48 vaccine products for the clinical trials described in Project 2. Crucell Holland BV is a medium-sized biotechnology company that is dedicated to the development of vaccines for infectious diseases. In particular, Crucell has pioneered the development of rAd vector-based vaccines and has developed vectors from Ad serotypes that have low seroprevalence in human populations. Crucell has also been a leader in the preclinical-to-clinical translational development of rAd vector-based vaccines for a variety of pathogens. In particular, Crucell has developed robust production and purification methods to manufacture clinical-grade rAd vaccines. Crucell has also standardized and validated release assays and has developed several packaging cell lines that support pharmaceutical-scale manufacturing in full compliance with Good Manufacturing Practice (GMP) guidelines. Vaccine candidates based on several different Ad serotypes have been manufactured and released by Crucell and have recently entered clinical trials for Ebola, malaria, and tuberculosis in both the United States and South Africa. Crucell will guarantee uniform, high quality manufacturing of the rAd vaccines as well as strict adherence to Standard Operating Procedures (SOPs) and rigorous quality control / quality assurance (QC/QA) standards in full compliance with all pertinent regulatory authorities. Research-grade vaccines will be provided for the GLP preclinical toxicology studies in rabbits, and clinical-grade vaccines will be manufactured for the phase 1 and phase 2a clinical trials described in Project 2. In our current IPCAVD AI066305 program, we have developed rAd26 and rAd5HVR48 GMP manufacturing processes and release assays that have already been approved by the FDA. In Project 3, we propose to utilize and to improve these existing production processes and analytical assays to manufacture and release the multivalent rAd26 and rAd5HVR48 clinical vaccine products. To accomplish these goals, we propose the following three Specific Aims: 1. To manufacture and release clinical-grade master virus seed stocks for rAd26 and rAd5HVR48 vectors expressing the optimal HIV-1 Gag-Nef, Pol, and Env antigens under GMP conditions; 2. To improve our current manufacturing processes for rAd26 and rAd5HVR48 vectors by optimizing vector yields at harvest and downstream purification steps; and 3. To manufacture, purify, release, and monitor the stability of trivalent, clinical-grade rAd26 and rAd5HVR48 vaccines expressing the optimal HIV Gag-Nef, Pol, and Env antigens under GMP conditions.

该项目的目的是使Crucell生产临床级硕士病毒种子​​库存 以及描述临床试验的三价临床级RAD26和RAD5HVR48疫苗产品 在项目2中。CrucellHolland BV是一家中型生物技术公司，致力于该公司 开发传染病的疫苗。特别是，克鲁塞尔（Crucell）开发了Rad的发展 基于向量的疫苗，并从血清型中的AD血清型中开发了较低的血清型 人口。 Crucell也一直是临床前翻译的领导者 基于RAD载体的各种病原体的疫苗。特别是，Crucell开发了强大的生产 和制造临床级RAD疫苗的纯化方法。 crucell也已经标准化了 经过验证的释放分析，并开发了几个包装细胞系来支持药物规模 制造完全符合良好的制造实践（GMP）指南。候选疫苗 基于几种不同的广告血清型已经由Crucell制造和发布，最近 在美国和南非参加了埃博拉病毒，疟疾和结核病的临床试验。 crucell将保证RAD疫苗的统一，高质量的制造以及严格 遵守标准操作程序（SOP）和严格的质量控制 /质量保证 （QC/QA）完全符合所有相关监管机构的标准。研究级疫苗会 为兔子的GLP临床前毒理学研究提供，临床级疫苗将是 针对项目2中描述的第1阶段和2A期临床试验制造。 在当前的IPCAVD AI066305程序中，我们开发了RAD26和RAD5HVR48 GMP FDA已经批准的制造过程和发布测定法。在项目3中 我们建议利用并改善这些现有的生产过程和分析测定 制造和释放多价RAD26和RAD5HVR48临床疫苗产品。到 实现这些目标，我们提出以下三个具体目标： 1。制造和释放RAD26和RAD5HVR48的临床级硕士病毒种子​​库存 在GMP条件下表达最佳HIV-1 GAG-NEF，POL和ENV抗原的载体； 2。通过优化，为了改善RAD26和RAD5HVR48矢量的当前制造过程 载体在收获和下游纯化步骤时产生；和 3。制造，纯化，释放和监视三价临床级RAD26和的稳定性 在GMP条件下表达最佳HIV GAG-NEF，POL和ENV抗原的RAD5HVR48疫苗。