Non-Viral Pandemic Influenza Vaccine Development

描述（由申请方提供）：为响应标题为“流感产品开发的合作研究伙伴关系”的RFA-AI-06-022，本申请拟实现旨在开发新型流感疫苗的特定目标。虽然通常对单个病毒亚型有效，但基于全流感病毒的疫苗难以快速制造，并且由于病毒表面抗原的抗原性转变和漂移而显示出对不同亚型的有限活性。此外，故意修改IAV可能会导致产生一种能够在有效疫苗开发之前促成人类大流行的病毒，其后果是前所未有的。通过开发疫苗技术，结合快速有效地将这些表位掺入新疫苗中的方法，可以大大改善抑制通过新的天然突变或有目的的操作产生的IAV感染的预防性方法，所述疫苗技术提供针对病毒感染的广泛保护。 为了满足这一需要，已经开发了一种免疫IAV的新方法，该方法将单层脂质体载体与能够被工程化以表达所选抗原表位的重组蛋白系统相结合。对于该项目，重组蛋白包含IAV M2蛋白的保守序列，该序列预期构建为代表各种IAV亚型。先前已证明该疫苗可刺激啮齿类动物的主动保护性应答，本提案的目的是开始与推进L-IAVM 2 e-HD候选疫苗进行临床试验相关的工艺开发活动。为了朝着这一目标取得进展，我们计划完成几个里程碑，包括：开发中试规模生产L-IAVM 2 e-HD疫苗所需的工艺和控制;证明使用新工艺生产L-IAVM 2 e-HD时，理化和生物学/免疫学特性不会发生变化。

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.