Immunogenicity of West Nile virus infectious DNA and its noninfectious derivatives.
The exceptionally high virulence of the West Nile NY99 strain makes its suitability in the development of a live WN vaccine uncertain. The aim of this study is to investigate the immunogenicity of noninfectious virus derivatives carrying pseudolethal mutations, which preclude virion formation without affecting preceding steps of the viral infectious cycle. When administered using DNA immunization, such constructs initiate an infectious cycle but cannot lead to a viremia. While the magnitude of the immune response to a noninfectious replication-competent construct was lower than that of virus or infectious DNA, its overall quality and the protective effect were similar. In contrast, a nonreplicating construct of similar length induced only a marginally detectable immune response in the dose range used. Thus, replication-competent noninfectious constructs derived from infectious DNA may offer an advantageous combination of the safety of noninfectious formulations with the quality of the immune response characteristic of infectious vaccines.
Seregin
Alexey
A
Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, USA.
Nistler
Ryan
R
Borisevich
Victoria
V
Yamshchikov
Galina
G
Chaporgina
Elena
E
Kwok
Chun Wai
CW
Yamshchikov
Vladimir
V
D000595:Amino Acid Sequence; D000818:Animals; D021461:Animals, Outbred Strains; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004279:DNA, Viral / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D010957:Plasmids; D011995:Recombination, Genetic; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014779:Virus Replication; D014901:West Nile Fever / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053060:West Nile Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*
D000914:Antibodies, Viral; D004279:DNA, Viral; D019444:Vaccines, DNA; D053060:West Nile Virus Vaccines