(787c) Development of a Scalable Process for Production of a Broadly Protective Influenza Antigen
AIChE Annual Meeting
2016
2016 AIChE Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Innovations in Biopharmaceutical Discovery, Development, and Manufacturing II
Friday, November 18, 2016 - 3:59pm to 4:21pm
A broadly protective influenza vaccine that would elicit strong protective responses for most or all possible circulating strains would dramatically reduce influenza-related hospitalizations and deaths by conferring life-long immunity. Our proposed vaccine would address many deficiencies in the current vaccine strategy by targeting a conserved region of the influenza hemagglutinin protein to protect against both seasonal and pandemic influenza strains. We will use a stabilized virus-like particle scaffold to present the antigen in a multivalent manner which more closely mimics the presentation of the antigen on the natural virus. By providing broadly protective immunity worldwide against seasonal and pandemic influenza, we would decrease the cost of medical care for influenza related illnesses, and dramatically reduce the number of influenza related deaths.
We have developed a stabilized hemagglutinin stem antigen which has the potential to provide broad protection against seasonal and pandemic strains of influenza. Here we discuss the development of a scalable refolding and formulation process for the production of our stabilized hemagglutinin stem antigen. By evaluating the kinetic and molecular forces required for the proper folding and trimerization of the hemagglutinin stem antigen, we have transitioned a number of lengthy, industrially unattractive refolding steps to a more reliable, scalable process. We are also working to further stabilize our hemagglutinin stem antigen for improved conformational stability with the ultimate goal of producing a cold-chain independent vaccine which would allow for improved distribution worldwide. We plan to evaluate both lyophilization and spray drying techniques for producing solid drug substance compatible with long term room temperature storage.