title: Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics.
abstract: Avian influenza A H5N1 viruses similar to those that infected humans in Hong Kong in 1997 continue to circulate in waterfowl and have reemerged in poultry in the region, raising concerns that these viruses could reappear in humans. The currently licensed trivalent inactivated influenza vaccines contain hemagglutinin (HA) and neuraminidase genes from epidemic strains in a background of internal genes derived from the vaccine donor strain, A/Puerto Rico/8/34 (PR8). Such reassortant candidate vaccine viruses are currently not licensed for the prevention of human infections by H5N1 influenza viruses. A transfectant H5N1/PR8 virus was generated by plasmid-based reverse genetics. The removal of the multibasic amino acid motif in the HA gene associated with high pathogenicity in chickens, and the new genotype of the H5N1/PR8 transfectant virus, attenuated the virus for chickens and mice without altering the antigenicity of the HA. A Formalin-inactivated vaccine prepared from this virus was immunogenic and protected mice from subsequent wild-type H5N1 virus challenge. This is the first successful attempt to develop an H5N1 vaccine seed virus resembling those used in currently licensed influenza A vaccines with properties that make it a promising candidate for further evaluation in humans.
authors.affiliation: Influenza Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. KSubbarao@cdc.gov
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.forename: Hualan
authors.initials: H
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Swayne
authors.forename: Louise
authors.initials: L
authors.lastname: Mingay
authors.forename: Ervin
authors.initials: E
authors.lastname: Fodor
authors.forename: George
authors.initials: G
authors.lastname: Brownlee
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xu
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Lu
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Katz
authors.forename: Nancy
authors.initials: N
authors.lastname: Cox
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsuoka
mesh_terms: D000818:Animals; D002645:Chickens; D005260:Female; D005289:Ferrets; D053124:Influenza A Virus, H5N1 Subtype; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D016865:Reassortant Viruses / Q000276:immunology*; D014162:Transfection; D014613:Vaccines, Attenuated / Q000276:immunology; D014779:Virus Replication
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated