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.