Development of a shelf-stable universal mucosal HA-vaccine for the prevention of influenza

PROJECT SUMMARY TFF Pharmaceuticals (TFFP) is developing a shelf-stable thin-film freeze (TFF) dry powder universal flu vaccine. Commercialization of this product would provide the first vaccine that is at least 75% effective against symptomatic influenza virus infection, with the added benefit of easy delivery and storage at room temperature to facilitate broad, cost-effective distribution. With NIAID’s Collaborative Influenza Vaccine Innovation Center funding, the University of Georgia (UGA) has developed a recombinant vaccine against all influenza virus hemagglutinin (HA) proteins and demonstrated its efficacy in mice and ferret models. If shown to be effective in humans, it could provide broad protection against both known and previously unrecognized strains of influenza virus, establishing a new standard of protection against seasonal viruses while heading off the emergence of novel strains in the future. A traditional liquid version of this vaccine would provide enormous benefits relative to the current seasonal vaccines, but they require cold-chain handling that increases costs and presents substantial barriers to establishing a stockpile or distributing the vaccine in underdeveloped areas. To address these challenges, UGA is collaborating with TFFP to develop a dry powder formulation of the universal vaccine. Using a thin-film freezing (TFF) technique, TFFP can formulate and manufacture dry powder vaccines that maintain immunogenicity while withstanding unintentional freezing. The vaccine powder can be stored and shipped free of cold-chain handling with extended stability for stockpiling. Our preliminary studies demonstrate that a reconstituted TFF-formulated version of UGA’s HA vaccine elicited the same level of immunogenicity and achieved the same protective efficacy as the original liquid vaccine in BALB/c mice. A follow up study in ferrets confirmed the efficacy of the TFF-HA vaccine in reducing viral titers in nasal swabs and preventing weight loss. In this Direct to Phase II SBIR, TFFP and UGA propose to evaluate different adjuvants for intranasal and pulmonary inhalation delivery and confirm the stability, immunogenicity, and efficacy of the TFF-formulated HA vaccine in ferrets, the gold standard for influenza virus vaccine testing (Aim 1). Aim 2 will scale-up manufacturing of the inhaled TFF-HA dry powder vaccine for subsequent toxicology studies in rats (Aim 3); we will also develop GMP formulation and manufacturing for clinical trials. This project is expected to provide all required IND- enabling studies to prepare an IND package and ultimately advance to human testing. A dry powder vaccine would eliminate challenges in shipping and storage, reducing the cost and complexity of vaccine stockpiles and vaccination campaigns. A shelf-stable universal influenza virus vaccine would also revolutionize the public health approach to influenza, providing a low-cost, broadly disseminable vaccine that is at least 75% effective against sympotmatic influenza virus infections regardless of which viral strain emerges each year.