title: A recombinant influenza A virus expressing domain III of West Nile virus induces protective immune responses against influenza and West Nile virus.
abstract: West Nile virus (WNV) continues to circulate in the USA and forms a threat to the rest of the Western hemisphere. Since methods for the treatment of WNV infections are not available, there is a need for the development of safe and effective vaccines. Here, we describe the construction of a recombinant influenza virus expressing domain III of the WNV glycoprotein E (Flu-NA-DIII) and its evaluation as a WNV vaccine candidate in a mouse model. FLU-NA-DIII-vaccinated mice were protected from severe body weight loss and mortality caused by WNV infection, whereas control mice succumbed to the infection. In addition, it was shown that one subcutaneous immunization with 10(5) TCID(50) Flu-NA-DIII provided 100% protection against challenge. Adoptive transfer experiments demonstrated that protection was mediated by antibodies and CD4+T cells. Furthermore, mice vaccinated with FLU-NA-DIII developed protective influenza virus-specific antibody titers. It was concluded that this vector system might be an attractive platform for the development of bivalent WNV-influenza vaccines.
authors.affiliation: Department of Virology, Erasmus MC, Rotterdam, The Netherlands. b.martina@erasmusmc.nl
authors.forename: Byron E E
authors.initials: BE
authors.lastname: Martina
authors.forename: Petra
authors.initials: P
authors.lastname: van den Doel
authors.forename: Penelope
authors.initials: P
authors.lastname: Koraka
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.forename: Gunther
authors.initials: G
authors.lastname: Spohn
authors.forename: Bart L
authors.initials: BL
authors.lastname: Haagmans
authors.forename: Lisette B V
authors.initials: LB
authors.lastname: Provacia
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D004285:Dogs; D006801:Humans; D007109:Immunity / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic / Q000235:genetics*; D013045:Species Specificity; D016896:Treatment Outcome; D014611:Vaccination; D014764:Viral Proteins / Q000737:chemistry* / Q000276:immunology; D015431:Weight Loss / Q000276:immunology; D014901:West Nile Fever / Q000276:immunology* / Q000821:virology; D053060:West Nile Virus Vaccines / Q000276:immunology; D014902:West Nile virus / Q000276:immunology*
chemical_list: D007252:Influenza Vaccines; D014764:Viral Proteins; D053060:West Nile Virus Vaccines