New Opportunities - Formulation of Francisella Live Attenuated Vaccine Strains

新机遇——弗朗西斯氏菌减毒活疫苗株的配制

• 批准号: 7680586
• 负责人: Eileen M. Barry
• 金额: $ 8.27万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7680586
• 关键词: Aerosols; Anthrax disease; Attenuated; Attenuated Live Virus Vaccine; Attenuated Vaccines; Awareness; Bacteria; Bacterial Vaccines; Biologic Characteristic; Biological; Biological Preservation; Breathing; Categories; Collaborations; Country; Data; Development; Devices; Disease; Drug Formulations; Event; Exposure to; Francisella; Francisella tularensis; Freeze Drying; Future; Goals; Human; Injection of therapeutic agent; Life; Liquid substance; Mus; Mutation; Oral; Organism; Parents; Pharmacologic Substance; Powder dose form; Process; Production; Property; Proxy; Range; Research Personnel; Resistance; Route; Scientist; Technology; Temperature; Testing; Time; Vaccines; Viral; Virulence; Virulent; Work; abstracting; aerosolized; base; biodefense; macrophage; new technology; novel; pathogen; reconstitution; response; success; sugar

Abstract Following the anthrax bioterror attacks in the US in 2001, awareness of the potentially devastating effects of attack with a bioweapon led to recognition of the need to take action and prepare against possible future nefarious events. F. tularensis was placed on the Category A select agent list as one of six pathogens that were of highest priority for the development of preventative countermeasures. Francisella tularensis can cause severe and fatal disease in humans if an aerosol containing as few as 10-100 CFU is inhaled. Indeed, in years past several countries weaponized F. tularensis for use as a possible biological weapon. Current work within the MARCE is underway to construct an optimal live vaccine based on introducing precisely defined attenuating mutations into a virulent Type A parent strain that will result in a vaccine that will confer strong protection against exposure to aerosolized virulent Type A F. tularensis. The successful live vaccine strain will eventually require rational formulation studies for application in mass production. It is prudent to begin formulation studies at this early point in the process, while new strains are under development, so that technology is ready for use for the final vaccine strain. With the goal of long term storage for this bioweapon vaccine, a dry powder formulation technology will be assessed. Aridis Pharmaceuticals has developed a novel technology for freeze dry foaming that has been used for the successful preservation of live viral and bacterial vaccines. Our studies will utilize the LVS strain as a proxy for the eventual Type A derivative strain. Aridis scientists will produce small scale bulk powder formulations of LVS that will be characterized at UMB for viability over temperature ranges, as well as biological properties of macrophage replication and mouse virulence. The resultant data will confirm the potential for the application of this formulation technology for use with Francisella live attenuated vaccine strains.

抽象的 2001 年美国发生炭疽生物恐怖袭击后，人们认识到生物武器袭击可能造成的破坏性影响，并认识到需要采取行动并为未来可能发生的邪恶事件做好准备。土拉弗朗西斯菌被列入 A 类选择病原体清单，作为制定预防对策最优先考虑的六种病原体之一。如果含有 10-100 CFU 的气溶胶被污染，土拉弗朗西斯菌就会对人类造成严重和致命的疾病。 吸入。事实上，在过去的几年里，一些国家将土拉杆菌武器化，用作可能的生物武器。 MARCE 目前正在进行的工作是构建一种最佳的活疫苗，该疫苗的基础是向强毒力 A 型亲本菌株中引入精确定义的减毒突变，从而产生一种疫苗，该疫苗将提供强有力的保护，防止暴露于雾化的强毒力 A 型土拉菌。成功的活疫苗株最终需要合理的配方研究才能大规模应用 生产。在新毒株正在开发的同时，在这一过程的早期阶段开始配方研究是明智的，这样技术就可以用于最终的疫苗毒株。为了长期储存这种生物武器疫苗，将评估干粉制剂技术。 Aridis Pharmaceuticals 开发了一种冷冻干燥发泡新技术，已用于成功保存活病毒和细菌疫苗。我们的研究将利用 LVS 菌株作为最终 A 型衍生菌株的代表。 Aridis 科学家将生产 LVS 的小规模散装粉末制剂，并将在 UMB 表征其在温度范围内的活力，以及巨噬细胞复制和小鼠毒力的生物学特性。由此产生的数据将证实该配方技术在弗朗西斯氏菌减毒活疫苗株中的应用潜力。