Protective Efficacy of a Chimeric Insect-Specific Flavivirus Vaccine against West Nile Virus

Virulent strains of West Nile virus (WNV) are highly neuro-invasive and human infection is potentially lethal. However, no vaccine is currently available for human use. Here, we report the immunogenicity and protective efficacy of a vaccine derived from a chimeric virus, which was constructed using the structural proteins (prM and E) of the Kunjin strain of WNV (WNV(KUN)) and the genome backbone of the insect-specific flavivirus Binjari virus (BinJV). This chimeric virus (BinJ/WNV(KUN)-prME) exhibits an insect-specific phenotype and does not replicate in vertebrate cells. Importantly, it authentically presents the prM-E proteins of WNV(KUN), which is antigenically very similar to other WNV strains and lineages. Therefore BinJ/WNV(KUN)-prME represents an excellent candidate to assess as a vaccine against virulent WNV strains, including the highly pathogenic WNV(NY99). When CD1 mice were immunized with purified BinJ/WNV(KUN)-prME, they developed robust neutralizing antibody responses after a single unadjuvanted dose of 1 to 5 μg. We further demonstrated complete protection against viremia and mortality after lethal challenge with WNV(NY99), with no clinical or subclinical pathology observed in vaccinated animals. These data suggest that BinJ/WNV(KUN)-prME represents a safe and effective WNV vaccine candidate that warrants further investigation for use in humans or in veterinary applications.