Characterization of West Nile virus live vaccine candidates attenuated by capsid deletion mutations.
Protein C deletion mutants of West Nile virus (WNV) were evaluated for their potential use as live virus vaccine candidates in vivo. Double and triple mutants carrying small deletions and second-site point mutations, as well as mutants with large deletions of 36 and 37 amino acid residues were tested in a stringent mouse challenge model. The mutant viruses were found to be non-pathogenic and to induce protective immunity in a wide range of inoculation doses (10(1)-10(6)FFU). Furthermore, the effects of combining three different previously identified resuscitating point mutations, as well as the combination of a large protein C deletion with a deletion mutation in the 3' non-coding region were studied. The data indicate that the production of safe and efficacious WNV live vaccines based on protein C deletion mutations is feasible.
Schlick
Petra
P
Intercell AG, Campus Vienna Biocenter 3, Vienna, Austria. pschlick@intercell.com
Kofler
Regina M
RM
Schittl
Beate
B
Taucher
Christian
C
Nagy
Eszter
E
Meinke
Andreas
A
Mandl
Christian W
CW
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins / Q000235:genetics*; D005260:Female; D006385:Hemagglutination Inhibition Tests; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000235:genetics; D017384:Sequence Deletion; D014774:Virulence; D014901:West Nile Fever / Q000276:immunology / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000235:genetics / Q000276:immunology*; D014902:West Nile virus / Q000235:genetics* / Q000472:pathogenicity
D000914:Antibodies, Viral; D036022:Capsid Proteins; D012367:RNA, Viral; D053060:West Nile Virus Vaccines