A Novel Cassette System for the Assembly of VLP Vaccines

描述（由申请人提供）：流感和其他传染病是美国和世界范围内死亡的主要原因。疫苗接种是预防这些疾病最具成本效益的策略。尽管在疫苗技术方面取得了很大进展，但疫苗的及时设计、验证和生产仍然是疫苗工业的一个主要障碍。亚单位疫苗表达重组方法的发展影响了开发时间和成本，但在引发免疫反应方面，亚单位疫苗往往不如病毒颗粒有效。病毒样颗粒或VLPs是弥补这一效力差距的一种方法，但VLPs的设计、表达和纯化仍然存在问题，而且利用现有技术难以开发帮助疫苗生产的统一工具。在这一提议中，我们描述了一种将重组蛋白整合到VLPs结构中的新型盒式技术。本提案中定义的原型系统将使用流感血凝素作为免疫原产生VLPs。VLP疫苗的效力将在动物身上进行测试，与单体血凝素进行比较。

DESCRIPTION (provided by applicant): Influenza and other infectious diseases are a major cause of death in the US and world-wide. Vaccination is the most cost-effective strategy to prevent these diseases. Although much progress has been made in vaccine technology, the timely design, validation and production of vaccines remains a major hurdle for the vaccine industry. The development of recombinant methods for the expression of subunit vaccines has impacted development timelines and costs but subunit vaccines frequently are not as potent as virus particles in eliciting an immune response. Virus like particles or VLPs represent one approach to bridge this potency gap but the design, expression and purification of VLPs remains problematic and the development of uniform tools to aid in vaccine production is elusive with existing technologies. In this proposal we describe a novel cassette technology of integrating recombinant proteins into the structure of VLPs. The prototype system defined in this proposal will generate VLPs using the influenza hemagglutinin as an immunogen. The potency of the VLP vaccine will be tested in animals in comparison to a monomeric hemagglutinin. PUBLIC HEALTH RELEVANCE: The influenza virus is highly infectious and causes both seasonal and pandemic outbreaks. A pandemic outbreak of a highly lethal strain would cause millions of deaths worldwide. Vaccines are the most cost- effective strategy to prevent infection. New strategies are required to produce more effective vaccines and to expedite the development time for new vaccines. Our goal is to develop a novel technology for the design and development of virus like particles that can be used in vaccines.