title: Complex adenovirus-mediated expression of West Nile virus C, PreM, E, and NS1 proteins induces both humoral and cellular immune responses.
abstract: West Nile Virus (WNV), a member of the family Flaviviridae, 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 (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 affecting 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 demonstrated that the antibodies were broadly neutralizing against both lineages of WNV, with a significant preference for 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 multiantigen approach may provide broad protection against multiple genetic variants of WNV.
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29403, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schepp-Berglind
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.forename: Danher
authors.initials: D
authors.lastname: Wang
authors.forename: Jason A
authors.initials: JA
authors.lastname: Wicker
authors.forename: Nicholas U
authors.initials: NU
authors.lastname: Raja
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hoel
authors.forename: David H
authors.initials: DH
authors.lastname: Holman
authors.forename: Alan D T
authors.initials: AD
authors.lastname: Barrett
authors.forename: John Y
authors.initials: JY
authors.lastname: Dong
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D036022:Capsid Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology* / Q000517:prevention & control; D053060:West Nile Virus Vaccines / Q000235:genetics / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology*
chemical_list: D036022:Capsid Proteins; C100315:NS1 protein, Flavivirus; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D053060:West Nile Virus Vaccines; C065696:glycoprotein E, Flavivirus