Development & Manufacture of an MDR Tuberculosis Vaccine

发展

• 批准号: 7010219
• 负责人: STEVEN GREGORY REED
• 金额: $ 409.56万
• 依托单位: ACCESS TO ADVANCED HEALTH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7010219
• 关键词: Mycobacterium tuberculosis; biotechnology; bioterrorism /chemical warfare; disease /disorder model; drug design /synthesis /production; guinea pigs; laboratory mouse; nonhuman therapy evaluation; tuberculosis; tuberculosis vaccines; vaccine development; vaccine evaluation

DESCRIPTION (provided by applicant): VACCINES FOR BIODEFENSE: We have identified several new TB vaccine candidate antigens based on human T cell responses and animal protection. Priority has been given to those that both elicit a Thl response from PBMC from PPD positive healthy donors and protect in rodent models. A non-human primate vaccine model has been established and is currently being used to further characterize vaccine candidates and adjuvant/delivery systems. We have developed Mtb72f in AS02A, the first defined TB vaccine to enter clinical trials. However, more recent data indicate that three other antigens may add to the protection obtained with Mtb 72f. Therefore, we have generated two additional polyproteins that incorporate these antigens on the Mtb72f backbone. The two new fusion proteins are Mtb92f and Mtbl 13f. Using validated rodent models of infection and disease we will select one of these antigens for GMP manufacture and clinical development. The selection process will emphasis both pre- and post-challenge immunization as criteria for prioritization. The selected candidate will be subjected to process development, including optimization of fermentation, development potency and stability assays of adjuvant (AS02A) formulated antigen. By the end of the funding period, we will have defined and developed a second generation vaccine candidate, collected data for MDR-TB, evaluated safety with a GLP toxicology study and manufactured vials under cGMPs. This will enable us to immediately proceed to human clinical trials after the end of the funding period.

描述（由申请人提供）：生物化疫苗的疫苗：我们根据人T细胞反应和动物保护确定了几种新的TB疫苗候选抗原。已经对那些引起PPD阳性供体PBMC响应的人的优先级和在啮齿动物模型中的保护。已经建立了非人类灵长类动物疫苗模型，目前正在用于进一步表征候选疫苗和辅助/递送系统。我们在AS02A中开发了MTB72F，这是第一个定义的结核病疫苗，用于进入临床试验。但是，最近的数据表明，其他三种抗原可能会增加使用MTB 72F获得的保护。因此，我们已经产生了两个将这些抗原掺入MTB72F主链上的多蛋白。这两个新的融合蛋白是MTB92F和MTBL 13F。使用经过验证的感染和疾病模型，我们将选择其中一种用于GMP制造和临床发育的抗原。选择过程将重点挑战前后免疫后作为优先级的标准。选定的候选者将受到过程开发的影响，包括优化发酵，发育效力和辅助（AS02A）制定抗原的稳定性测定。到资金期结束时，我们将定义并开发了第二代疫苗候选者，收集了MDR-TB的数据，通过GLP毒理学研究评估了安全性，并在CGMP下进行了制造的小瓶。这将使我们能够在资金结束后立即进行人类临床试验。