New Opportunities - Formulation of Francisella Live Attenuated Vaccine Strains

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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.