New Opportunities Projects
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Novel Vaccine Technology for Biodefense
Collaborating Institution: University of Texas Medical Branch at Galveston (UTMB), Galveston, TX
Principal Investigator: Scott Weaver, PhD
Consultants: a)
Lada Rasochova, PhD – Dow Chemical Company, San Diego,
CA Expected Product: Technology to rapidly produce and deploy effective vaccines.
Description: This project will develop a platform technology capable of rapidly producing virus-like particle (VLP) vaccines in a non-mammalian bacterial system that protects 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 for protecting researchers and first responders. However, developing safe and effective vaccines with current methods 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 to be inherently safer than whole organism vaccines because they lack all functionality associated with infection and 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-based technology for the synthesis of foreign antigenic epitopes in cowpea chlorotic mottle virus VLPs to develop this platform for use in rapidly developing vaccines against emerging and biothreat agents. The methods developed and validated in this process will comprise a rapid response approach for reacting to newly discovered or weaponized viruses. To develop this novel vaccine platform technology, we will use eastern equine encephalitis virus (EEEV), an NIAID Category B agent that has undergone very little antigenic characterization. Although an experimental formalin-inactivated vaccine elicits neutralizing antibodies to the two envelope proteins (E1 and E2) in vaccinated humans, the protective epitopes are unknown. Thus, EEEV will be used to evaluate the ability of the new platform technology to produce vaccine candidates rapidly against poorly characterized or newly discovered viruses.
We will prepare envelope protein epitope libraries from EEEV cDNA in the bacterial VLP system, develop a high throughput screening method to identify suitable vaccine candidates that are recognized by antibodies from immune animals, and select a panel of VLPs to vaccinate relevant, small animal models. Epitopes found to provide protection will eventually be tested in larger animals prior to moving into a pre-clinical nonhuman primate test. This methodology will evolve a response mechanism capable of quickly reacting to new or bioengineered viruses to rapidly produce and deploy effective vaccines.
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