Powassan virus is a flavivirus that can be transmitted by at least six tick species within the Ixodes and Dermacentor families, and can cause severe encephalitis and neurologic sequelae. It is the only tick-borne flavivirus endemic in North America. West Nile virus, also a flavivirus, is mostly transmitted by Culex mosquitoes, has a broad host range, and can cause encephalitis or meningitis associated with lengthy patient recovery. No human vaccine is currently available for either disease. The contractor will generate novel subunit vaccines, applying the lessons learned from their previous work with other flavivirus vaccines, and formulate it with Alhydroxiquim-II, an adjuvant that is used in the Covaxin COVID vaccine.