title: An attenuated West Nile prototype virus is highly immunogenic and protects against the deadly NY99 strain: a candidate for live WN vaccine development.
abstract: In a short time, West Nile virus has developed into a nationwide health and veterinary problem. The high virulence of the circulating virus and related lineage 1 WN strains hinders development of an attenuated live vaccine. We describe an attenuated WN isolate, WN1415, which is a molecularly cloned descendant of the WN prototype B956 strain. The parent virus belongs to lineage 2, members of which have not been associated with epidemic or epizootic outbreaks. A set of non-conservative mutations, mostly in non-structural protein genes, distinguishes the WN1415 isolate from the parent B956 prototype strain. Immunization with WN1415 (55-550,000 pfu) established a potent immunity, which protected the majority of mice against lethal challenge with WN NY99. The attenuated nature of the isolate and its excellent growth characteristics combined with the availability of a highly stable infectious clone make the isolate an attractive candidate for live WN vaccine development.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Galina
authors.initials: G
authors.lastname: Yamshchikov
authors.forename: Victoria
authors.initials: V
authors.lastname: Borisevich
authors.forename: Alexey
authors.initials: A
authors.lastname: Seregin
authors.forename: Elena
authors.initials: E
authors.lastname: Chaporgina
authors.forename: Margarita
authors.initials: M
authors.lastname: Mishina
authors.forename: Vasiliy
authors.initials: V
authors.lastname: Mishin
authors.forename: Chun Wai
authors.initials: CW
authors.lastname: Kwok
authors.forename: Vladimir
authors.initials: V
authors.lastname: Yamshchikov
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003062:Codon / Q000235:genetics; D016384:Consensus Sequence; D006224:Cricetinae; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D009500:Neutralization Tests; D014613:Vaccines, Attenuated; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000737:chemistry / Q000235:genetics; D014901:West Nile Fever / Q000276:immunology*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology*
chemical_list: D003062:Codon; D014613:Vaccines, Attenuated; D014765:Viral Vaccines