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 遵循2001年美国在美国发动炭疽病的攻击之后，意识到对生物武器的攻击潜在毁灭性影响的认识，导致人们认识到需要采取行动并为可能未来的邪恶事件做准备。将tularensis置于选择剂列表上，作为六种病原体之一，在预防性对策的发展中占优先。如果含有10-100 CFU的气溶胶是，francisella tularensis会导致人类严重和致命疾病 吸入。的确，过去几个国家的几年中，将tularensis武器武器用作可能的生物武器。 MARCE内的当前工作正在进行中，以建造一种基于将精确定义的衰减突变引入毒性型A型A型菌株的最佳活疫苗，该疫苗将导致一种疫苗，该疫苗将赋予强大的保护，以防止暴露于雾化的毒素型A型A型。成功的实时疫苗菌株最终将需要合理制定研究以应用于质量 生产。在此过程的早期开始，在开发新菌株的同时，谨慎地开始制定研究，以便可以将技术用于最终的疫苗菌株。为了为这种生物武器疫苗长期存储，将评估一种干粉配方技术。 Aridis Pharmaceuticals开发了一种新型技术，用于冻结干泡沫，该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型衍生物菌株的代理。 ARIDIS科学家将生产LVS的小规模粉末配方，在UMB上以温度范围的生存能力以及巨噬细胞复制和小鼠毒力的生物学特性。最终的数据将确认将这种配方技术应用于Francisella Live衰减疫苗菌株的可能性。