title: A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF+ cells.
abstract: In this study, a recombinant truncated West Nile virus envelope protein antigen (rWNV-E) was produced in serum-free cultures of the expresSF+ insect cell line via baculovirus infection. This production system was selected based on its use in the production of candidate human and animal vaccine antigens. A defined fermentation and purification process for the rWNV-E antigen was established to control for purity and immunogenicity of each protein batch. The material formulated with aluminum hydroxide was stable for greater than 8months at 4 degrees C. The recombinant vaccine candidate was evaluated for immunogenicity and protective efficacy in several animal models. In mouse and hamster WNV challenge models, the vaccine candidate induced viral protection that correlated with anti-rWNV-E immunogenicity and WNV neutralizing antibody titers. The rWNV-E vaccine candidate was used to boost horses previously immunized with the Fort Dodge inactivated WNV vaccine and also to induce WNV neutralizing titers in naïve foals that were at least 14weeks of age. Furthermore, the vaccine candidate was found safe when high doses were injected into rats, with no detectable treatment-related clinical adverse effects. These observations demonstrate that baculovirus-produced rWNV-E can be formulated with aluminum hydroxide to produce a stable and safe vaccine which induces humoral immunity that can protect against WNV infection.
authors.affiliation: L2 Diagnostics, LLC, 300 George Street, New Haven, CT 06511, USA. nathalie.bonafe@L2dx.com
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bonafé
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Rininger
authors.forename: Richard G
authors.initials: RG
authors.lastname: Chubet
authors.forename: Harald G
authors.initials: HG
authors.lastname: Foellmer
authors.forename: Stacey
authors.initials: S
authors.lastname: Fader
authors.forename: John F
authors.initials: JF
authors.lastname: Anderson
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Bushmich
authors.forename: Karen
authors.initials: K
authors.lastname: Anthony
authors.forename: Michel
authors.initials: M
authors.lastname: Ledizet
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Koski
authors.forename: Paul
authors.initials: P
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016367:Baculoviridae / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D004195:Disease Models, Animal; D006734:Horse Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006736:Horses; D006801:Humans; D051379:Mice; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018411:Spodoptera / Q000378:metabolism* / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014901:West Nile Fever / Q000276:immunology / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D053060:West Nile Virus Vaccines