Good Manufacturing Practices Master Cell and Working Cell Banks and GMP Pilot Lot of Prototype Shigella flexneri 2a live vector expressing enterotoxigenic E. coli antigens, CVD 1208S 122

良好生产规范主细胞和工作细胞库以及表达产肠毒素大肠杆菌抗原的福氏志贺氏菌 2a 活载体原型 GMP 中试批次，CVD 1208S 122

• 批准号: 9363198
• 负责人: Eileen M. Barry
• 金额: $ 96.38万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-08 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9363198
• 关键词: Address; Animal Model; Antigens; Attenuated; Categories; Cells; Chemistry; Child; Chromosomes; Cities; Clinical; Clinical Trials; Colony-forming units; Combined Vaccines; Contracts; Data; Developing Countries; Development; Disease; Engineering; Enterotoxins; Excretory function; Fermentation; Formulation; Freezing; Funding; Future; Genes; Goals; Grant; Guidelines; Human; I-antigen; Immune response; In Vitro; Industrialization; Investigational Drugs; Investigational New Drug Application; Laboratory Research; Lead; Licensure; Manufacturer Name; Methods; Mission; Organism; Pattern; Performance; Phase; Phase I Clinical Trials; Preparation; Process; Production; Redwood; Running; Safety; Series; Services; Shigella; Shigella flexneri; Technology Transfer; Testing; Translating; Translations; Traveler' s diarrhea; United States Food and Drug Administration; Vaccines; Vial device; Vibrio cholerae O1; Visit; Vulnerable Populations; Work; Writing; cell bank; colonization factor antigens; enterotoxigenic Escherichia coli; immunogenicity; in vivo; liquid formulation; oral vaccine; paragon; pathogen; pilot lot production; portion control; pre-clinical; preclinical study; prevent; prototype; research clinical testing; scale up; vaccine candidate; vaccine development; vector

Project Summary /Abstract Shigella and enterotoxigenic Escherichia coli (ETEC) are two of the most important diarrheal pathogens worldwide, causing moderate-to-severe diarrheal disease in young children in developing countries and travelers' diarrhea among U.S. travelers who visit developing countries. We have developed a lead candidate prototype Shigella-enterotoxigenic Escherichia coli (ETEC) vaccine candidate strain, CVD 1208S-122, which consists of an attenuated ∆guaBA,∆set,∆sen Shigella flexneri 2a strain engineered to express ETEC colonization factor antigen I (CFA/I) and the B and A2 subunits of heat-labile enterotoxin (LThA2B) from genes integrated into the chromosome. In animal models this prototype has elicited protective immune responses against these two important human diarrheal pathogens. The overall goal of this proposal is to translate this prototype Shigella-ETEC vaccine construct from an academic research laboratory vaccine candidate to a potential human vaccine ready to enter Phase 1 clinical trials (under other funding) to evaluate its safety, clinical tolerability, excretion pattern, transmissibility to close contacts, and immunogenicity. We have engaged an industrial partner, PaxVax, Inc. of Redwood City, CA. PaxVax is committed to becoming a future manufacturer of our multivalent combination vaccine and will provide overall strategic guidance for this translation, including regulatory support (in preparation of the chemistry/manufacture/control (CMC) portion of the IND, advice on interaction with contract manufacturing organizations (CMOs), and other industrial know- how. To accomplish this transition from promising research laboratory candidate to potential human trial, we propose the following activities. Aim 1. Technology transfer, Cell Bank production, process development and pilot scale-up of Shigella-ETEC vaccine candidate CVD 1208S-122. Aim 2: Comprehensive cGMP pilot production lot to provide 3000 vials of CVD 1208S-122. Aim 3: Comprehensive pre-clinical studies on the cGMP pilot lot formulation of CVD 1208S-122 to underpin submission of an IND to the FDA to prepare for Phase 1 and 2 clinical trials.

项目摘要 /摘要 志贺氏菌和肠毒素大肠杆菌（ETEC）是最重要的腹泻病原体 在全球范围内，在发展中国家和 旅行者在访问发展中国家的美国旅行者中的腹泻。 原型志贺氏菌 - 体毒素大肠杆菌（ETEC）疫苗候选菌株，CVD 1208S-122，其中 由一个减弱的∆ guaba，∆集，ΔSen志贺氏弹性2a 2a应变为表达ETEC 来自基因的抗原因子I（CFA/I）和热量肠毒素（LTHA2B）的B和A2亚基 在动物模型中整合到染色体中。 反对重要的人腹泻病原体。 原型志贺氏菌疫苗构造从候选学术研究实验室疫苗到 潜在的人类疫苗准备进入1期临床试验（根据其他资金）来评估其安全性， 我们参与了。 加利福尼亚州雷德伍德市的工业合作伙伴Paxvax，Inc。 我们多价组合疫苗的制造商，将为此提供总体战略指导。 翻译，包括监管支持（准备化学/制造/控制（CMC）部分 IND，与合同制造组织（CMO）互动的建议以及其他工业知识 - 如何实现从有前途的研究实验室候选人到潜在的人类试验的过渡 提出以下活动。 目的1。志贺氏菌 - 伊斯克的技术转移，细胞银行生产，过程开发和试点规模 疫苗候选CVD 1208S-122。 AIM 2：全面的CGMP飞行员生产批次提供3000瓶CVD 1208S-122。 目标3：关于CGMP飞行员批次CVD 1208S-122的全面临床前研究 提交印度FDA的提交准备1阶段和2阶段的临床试验。