title: An inactivated West Nile Virus vaccine derived from a chemically synthesized cDNA system.
abstract: A cDNA comprising the complete genome of West Nile Virus (WNV) was generated by chemical synthesis using published sequence data, independent of any preformed viral components. The synthetic WNV, produced by transfection of in vitro transcribed RNA into cell culture, exhibited undistinguishable biological properties compared to the corresponding animal-derived wild-type virus. No differences were found concerning viral growth in mammalian and insect cell lines and concerning expression of viral proteins in cells. There were also no significant differences in virulence in mice following intranasal challenge. After immunizations of mice with experimental vaccines derived from the synthetic and wild-type viruses, protection from lethal challenge was achieved with similar amounts of antigen. Both vaccine preparations also induced comparable levels of neutralizing antibodies in mice. In addition, the synthetic approach turned out to be very accurate, since the rescued WNV genome contained no undesired mutations. Thus, the first flavivirus based on chemical gene synthesis was indistinguishable from the parent virus. This demonstrates that virus isolates from animal sources are dispensable to derive seed viruses for vaccine production or research.
authors.affiliation: Baxter Bioscience, Biomedical Research Center, Uferstrasse 15, A-2304 Orth/Donau, Austria.
authors.forename: Klaus K
authors.initials: KK
authors.lastname: Orlinger
authors.forename: Georg W
authors.initials: GW
authors.lastname: Holzer
authors.forename: Julia
authors.initials: J
authors.lastname: Schwaiger
authors.forename: Josef
authors.initials: J
authors.lastname: Mayrhofer
authors.forename: Karl
authors.initials: K
authors.lastname: Schmid
authors.forename: Otfried
authors.initials: O
authors.lastname: Kistner
authors.forename: P
authors.initials: P
authors.lastname: Noel Barrett
authors.forename: Falko G
authors.initials: FG
authors.lastname: Falkner
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics*; D005260:Female; D016679:Genome, Viral; D007313:Insecta; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000235:genetics; D016019:Survival Analysis; D014162:Transfection; D015164:Vaccines, Inactivated / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D014774:Virulence; D014901:West Nile Fever / Q000517:prevention & control*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018076:DNA, Complementary; D012367:RNA, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines