Development of adenovirus-based West Nile Virus vaccines

West Nile Virus (WNV), a member of the Flaviviridae family, was first identified in Africa in 1937. In recent years, it has spread into Europe and North America. The clinical manifestations of WNV infection range from mild febrile symptoms to fatal encephalitis. Two genetic lineages (I and II) are recognized; lineage II is associated with mild disease while lineage I is generally associated with more severe disease, including encephalitis. WNV has now spread across North America, significantly impacting both public and veterinary health.;In the efforts to develop an effective vaccine against all genetic variants of WNV, we have studied the feasibility of inducing both neutralizing and cellular immune responses by de novo synthesis of WNV antigens using a recombinant complex adenoviral vaccine (cAdVax) vectors. We developed separate vaccine vectors from the Lineage I and Lineage II WNV proteins and further combined them into a bivalent vaccine. In addition, the vaccine vectors express both structural and nonstructural proteins. Therefore, this enables the vaccines to induce both humoral and cellular immune responses.;By vaccinating mice, we demonstrated that multiple antigens synthesized de novo from our cAdVax-WNV vectors are capable of inducing both arms of the immune response, humoral and cellular. Specifically, we found that the conserved nonstructural antigens induced higher cellular immune responses than the membrane glycoproteins. Furthermore, the neutralization assays demonstrated that the antibodies were broadly neutralizing against both lineages of the WNV, with a significant preference towards the homologous lineage virus. The bivalent, multi-antigen approach provided a broad protection against multiple genetic variants of WNV meaning that it did not show preference towards any one lineage.