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WRCE Theme 2: Vaccine Development for Arboviral and Emerging Viral Diseases

Theme Leader: Scott Weaver, PhD – University of Texas Medical Branch, Galveston, TX

Expected Product: The proposed projects in Theme 2 will develop improved vaccine technologies to both protect the US population against these emerging viral diseases, and mitigate endemic transmission in tropical locations that increases our risk of importation.

Description: The continued emergence of highly pathogenic RNA viruses represents a severe threat to human health. Among the most important emerging pathogens are the arthropod-borne viruses (arboviruses) that comprise a taxonomically diverse group of agents that share vector-borne transmission. Nearly all arboviruses that cause human disease belong to three families: (1) the genus Flavivirus in the family Flaviviridae; (2) the genus Alphavirus in the family Togaviridae; and (3) several genera in the family Bunyaviridae. Most of these viruses are zoonotic and utilize mosquitoes or ticks for transmission among wild animals. Humans usually become infected when amplification in the zoonotic cycle leads to “spillover.” Arboviral infections are therefore particularly difficult to prevent because the wild animal reservoir hosts and enzootic arthropod vectors cannot be controlled in an environmentally acceptable manner. Reemerging viral diseases, including Argentine hemorrhagic fever, and emerging viral disease such as Nipah virus infection, are also of major public health importance. The activities of this theme are devoted to developing live attenuated vaccines and improved animal models for alphaviruses, building upon our expertise in arboviral genetics; determining the mechanism of attenuation for MP-12, the vaccine strain for Rift Valley fever virus (RVFV); identifying human CD8 epitopes for RVFV to include in new RVFV vaccines; developing a reverse genetics system for Junin virus; producing Nipah virus-like particles for use as protective immunogens; and determining the structural characteristics using cryoEM to improve the RepliVAX vaccine for Japanese encephalitis virus.