Non-Viral Pandemic Influenza Vaccine Development

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DESCRIPTION (provided by applicant): In response to RFA-AI-06-022 entitled "Cooperative Research Partnerships for Influenza Product Development" this application proposes to achieve specific Milestones aimed at developing a novel influenza vaccine. While generally effective against individual viral subtypes, whole influenza virus-based vaccines are difficult to manufacture rapidly and demonstrate limited activity against different subtypes due to antigenic shift and drift in the surface antigens of the virus. In addition, deliberate modifications of IAV could result in the production of a virus capable of precipitating a human pandemic with unprecedented consequences before effective vaccines could be developed. Preventative methods for inhibiting infection with IAV created through new, natural mutations or purposeful manipulations, would be greatly improved by the development of vaccine technologies that provide for broad protection against viral infection combined with a method to rapidly and effectively incorporate these epitopes into new vaccines. In response to this need, a new approach to immunization for IAV has been developed that combines a unilamellar liposome carrier with a recombinant protein system that is capable of being engineered to express selected antigenic epitopes. For this project, the recombinant protein incorporates a conserved sequence of the IAV M2 protein prospectively constructed to represent a variety of IAV subtypes. It has been previously shown that this vaccine stimulates active protective responses in rodents and the objective of the present proposal is to begin the process development activities associated with advancing a L-IAVM2e-HD vaccine candidate towards clinical testing. In order to make progress towards this goal, we plan to complete several Milestones including: developing the processes and controls necessary to manufacture a L-IAVM2e-HD vaccine in pilot scale quantities and; demonstrating that the physicochemical and biological/immunological properties do not change when a L-IAVM2e-HD are produced using the new processes.