New Opportunities - Formulation of Francisella Live Attenuated Vaccine Strains

摘要 2001年美国发生炭疽热生物恐怖袭击后，人们认识到生物武器袭击的潜在破坏性影响，从而认识到需要采取行动，为未来可能发生的邪恶事件做好准备。F.土拉热菌作为开发预防对策的最高优先级的六种病原体之一被列入A类选择剂清单。如果含有少至10-100 CFU的气溶胶被吸入，则土拉热弗朗西丝菌可在人类中引起严重和致命的疾病。 吸入。事实上，在过去的几年里，有几个国家将F。土拉热菌可能被用作生物武器MARCE目前的工作正在进行中，以构建一种最佳的活疫苗，其基础是将精确定义的减毒突变引入到强毒A型亲本菌株中，这将产生一种疫苗，该疫苗将对暴露于气溶胶化的强毒A型F型提供强有力的保护。土拉热。成功的活疫苗株最终将需要进行合理的配方研究，以便大规模应用 生产谨慎的做法是在工艺的早期阶段开始制剂研究，同时新菌株正在开发中，以便技术可用于最终疫苗菌株。为了长期储存这种生物武器疫苗，将对干粉制剂技术进行评估。Aridis Pharmaceuticals开发了一种用于冷冻干燥发泡的新技术，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的科学家将生产LVS的小规模散装粉末制剂，这些制剂将在UMB进行温度范围内的生存能力以及巨噬细胞复制和小鼠毒力的生物学特性的表征。所得数据将证实该制剂技术应用于弗朗西斯菌减毒活疫苗株的潜力。

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.