This project will develop a platform technology capable of rapidly producing virus-like particle vaccines, in anon-mammalian bacterial system, that protect people against infection by emerging or biothreat viruses.Vaccination is often the only line of biodefense for civilian and military personnel, and an important tool forprotecting researchers and first responders. However, developing safe and effective vaccines with currentmethods based on live-attenuated or killed viruses cultured in mammalian cells is a highly regulated,uncertain and slow process requiring many years. Subunit or peptide-based vaccines are expected beinherently safer than whole organism vaccines because they lack all functionality associated with infectionand pathogenesis, and contain only that segment(s) of an antigen that is known to be effective.We will exploit recent advances by the Dow Chemical Company in a high expression, bacterial protein-basedtechnology for the synthesis of foreign antigenic epitopes in cowpea chlorotic mottle virus (CCMV) virus-likeparticles (VLPs) to develop this platform for use in rapidly developing vaccines against emerging andbiothreat agents. The methods developed and validated in this process will comprise a rapid responseapproach for reacting to newly discovered or weaponized viruses. To develop this novel vaccine platformtechnology, we will use Eastern Equine Encephalitis virus (EEEV, NIAID Category B), which has receivedvery little antigenic characterization. Although an experimental formalin-inactivated vaccine elicitsneutralizing antibodies to the two envelope proteins (E1 and E2) in vaccinated humans, the protectiveepitopes are unknown. Thus, EEEV will be used to evaluate the ability of the new platform technology torapidly produce vaccine candidates against poorly characterized or newly discovered viruses.We will prepare envelope protein epitope libraries from EEEV cDNA in the bacterial VLP system, develop ahigh throughput screening method to identify suitable vaccine candidates that are recognized by antibodiesrom immune animals, and select a panel of VLPs to vaccinate relevant, small animal models. Epitopesfound to provide protection will eventually be tested in larger animals prior to moving into a pre-clinical nonhumanprimate test. This methodology will evolve a response mechanism capable of quickly reacting to newor bioengineered viruses to rapidly produce and deploy effective vaccines.
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