A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF plus cells

被引:24
作者
Bonafe, Nathalie [1 ]
Rininger, Joseph A. [2 ]
Chubet, Richard G. [2 ]
Foellmer, Harald G. [3 ]
Fader, Stacey [1 ]
Anderson, John F. [4 ]
Bushmich, Sandra L. [5 ]
Anthony, Karen [1 ]
Ledizet, Michel [1 ]
Fikrig, Erol [3 ]
Koski, Raymond A. [1 ]
Kaplan, Paul [1 ]
机构
[1] L2 Diagnost LLC, New Haven, CT 06511 USA
[2] Prot Sci Corp, Meriden, CT 06450 USA
[3] Yale Univ, Sch Med, Infect Dis Sect, New Haven, CT 06520 USA
[4] Connecticut Agr Expt Stn, New Haven, CT 06504 USA
[5] Univ Connecticut, Dept Pathobiol, Storrs, CT 06269 USA
关键词
West Nile virus; Envelope protein; Vaccine; Baculovirus; ExpresSF plus insect cells; LIVE-ATTENUATED VACCINE; PRECLINICAL EVALUATION; NEUTRALIZING ANTIBODY; PROTECTIVE EFFICACY; CRYSTAL-STRUCTURE; SECRETED FORM; INSECT CELLS; MICE; IMMUNOGENICITY; IMMUNIZATION;
D O I
10.1016/j.vaccine.2008.10.046
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 8 months at 4 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 naive foals that were at least 14 weeks 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. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:213 / 222
页数:10
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