Non-Viral Pandemic Influenza Vaccine Development

描述（由申请人提供）：作为对题为“流感产品开发合作研究伙伴关系”的RFA-AI-06-022的回应，本申请提出实现旨在开发新型流感疫苗的特定里程碑。虽然一般对个别病毒亚型有效，但基于流感病毒的全疫苗很难快速生产，并且由于病毒表面抗原的抗原转移和漂移，对不同亚型的活性有限。此外，在研制出有效的疫苗之前，有意修改内源性病毒可能导致产生一种能够引发人类大流行的病毒，造成前所未有的后果。通过新的自然突变或有目的的操作创造的抑制内源性病毒感染的预防方法，将通过疫苗技术的发展得到极大的改进，这些疫苗技术可提供广泛的病毒感染保护，并结合一种快速有效地将这些表位纳入新疫苗的方法。

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.