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Clin. Vaccine Immunol. doi:10.1128/CVI.00070-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Complex Adenovirus-mediated expression of C, PreM, E, and NS1 proteins of West Nile Virus induces both humoral and cellular immune responses

Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC, 29403; Division of Biodefense Vaccines, GenPhar Inc., 871 Lowcountry Blvd., Mount Pleasant, SC 29464; Departments of Pathology and Microbiology & Immunology, Sealy Center for Vaccine Development, and Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas TX 77555-0609

	Abstract

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 has been associated with 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 complex adenoviral vaccine (CAdVax) vector. By expressing multiple WNV proteins from a single vaccine vector, we were able to induce both humoral and cellular immune responses in vaccinated mice. Neutralization assays demonstrate that the antibodies were broadly neutralizing against both lineages of the WNV, with a significant preference towards the homologous lineage II virus.

The results from this study show that multiple antigens synthesized de novo from a CAdVax vector are capable of inducing both humoral and cellular immune responses against WNV, and that a multi-antigen approach may provide broad protection against multiple genetic variants of WNV.

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