Structural and Antigenic Features of Powassan Virus Envelope Protein

Abstract Flaviviruses, such as West-Nile virus and Dengue virus, are insect-transmitted positive-sense RNA viruses that cause substantial morbidity and mortality worldwide. Powassan virus is an emerging encephalitic tick-borne flavivirus endemic to the northern United States, and is currently the only tick-transmitted flavivirus known to infect humans in North America. In cases of severe neurological disease, up to 10% of patients die of Powassan encephalitis, while many survivors are left with long-term neurological sequelae. Despite this, no vaccines or therapeutics are currently available to treat Powassan virus infection. Flaviviral vaccination efforts are commonly foiled by an inability to generate potent neutralizing responses, and by genesis of cross-reactive antibodies that paradoxically enhance infection by heterologous flaviviruses. These neutralizing antibodies, and their cross-reactive counterparts, commonly target structurally homologous epitopes present on many flaviviruses. Thus, understanding these epitopes has important implications for vaccine design. Little is known about the structure of Powassan virus envelope protein or host antibodies that target it. We have recombinantly expressed Powassan virus envelope protein and are currently working to determine its structure. As well, a panel of Powassan-virus specific monoclonal antibodies has been developed. Utilizing our recombinant protein, we are characterizing the epitopes these antibodies utilize as well as their biochemical and functional properties. These findings will aid vaccine and therapeutic design for Powassan virus and expand our understanding of the quintessential antigenic and structural features of flaviviral envelope proteins.