Construction and characterization of a second-generation pseudoinfectious West Nile virus vaccine propagated using a new cultivation system.
Safer vaccines are needed to prevent flavivirus diseases. To help develop these products we have produced a pseudoinfectious West Nile virus (WNV) lacking a functional C gene which we have named RepliVAX WN. Here we demonstrate that RepliVAX WN can be safely propagated at high titer in BHK cells and vaccine-certified Vero cells engineered to stably express the C protein needed to trans-complement RepliVAX WN growth. Using these BHK cells we selected a better growing mutant RepliVAX WN population and used this to generate a second-generation RepliVAX WN (RepliVAX WN.2). RepliVAX WN.2 grown in these C-expressing cell lines safely elicit strong protective immunity against WNV disease in mice and hamsters. Taken together, these results indicate the clinical utility of RepliVAX WN.2 as a vaccine candidate against West Nile encephalitis.
Widman
Douglas G
DG
Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
Ishikawa
Tomohiro
T
Fayzulin
Rafik
R
Bourne
Nigel
N
Mason
Peter W
PW
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017353:Gene Deletion; D051379:Mice; D009500:Neutralization Tests; D016019:Survival Analysis; D014764:Viral Proteins / Q000235:genetics; D014901:West Nile Fever / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000235:genetics* / Q000276:immunology*; D014902:West Nile virus / Q000235:genetics* / Q000254:growth & development*
D000914:Antibodies, Viral; D014764:Viral Proteins; D053060:West Nile Virus Vaccines