title: Development of Eurasian H7N7/PR8 high growth reassortant virus for clinical evaluation as an inactivated pandemic influenza vaccine.
abstract: Avian-to-human transmission of the high pathogenicity (HP) H7N7 subtype avian influenza viruses in the Netherlands during 2003 caused zoonotic infections in 89 people, including a case of acute fatal respiratory distress syndrome. Public health emergency preparedness against H7N7 avian influenza viruses with pandemic potential includes the development of vaccine candidate viruses. In order to develop a high growth reassortant vaccine candidate virus, low pathogenicity (LP) A/mallard/Netherlands/12/2000 (H7N3) and A/mallard/Netherlands/2/2000 (H10N7) strains were selected as donors of the H7 haemagglutinin and N7 neuraminidase genes, respectively. The donor viruses exhibited high amino acid sequence homology with the surface glycoproteins of A/Netherlands/219/03 H7N7 virus (NL219), an isolate recovered from the fatal human case. Adhering to the seasonal influenza vaccine licensure regulations, we generated a H7N7/PR8 reassortant containing desired surface glycoprotein genes from the mallard viruses and internal genes of A/Puerto Rico/8/34 human vaccine strain (H1N1). Antigenic analysis revealed that the vaccine candidate virus confers broad antigenic cross-reactivity against contemporary Eurasian and the North American H7 subtype human isolates. Mice immunized with formalin inactivated (FI) H7N7/PR8 whole virus vaccine with or without aluminum hydroxide adjuvant conferred clinical protection from mortality and reduced pulmonary replication of the NL219 challenge virus. The FI H7N7/PR8 whole virus vaccine also afforded cross-protection in mice at the pulmonary level against antigenically distinct North American LP A/Canada/444/04 (H7N3) human isolate. The vaccine candidate virus satisfied the agricultural safety requirements for chickens, proved safe in mice, and has entered in phase-I human clinical trial in the United States.
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, NE, Atlanta, GA 30333, USA. Samadhan.Jadhao@ars.usda.gov
authors.forename: Samadhan J
authors.initials: SJ
authors.lastname: Jadhao
authors.forename: Jenna
authors.initials: J
authors.lastname: Achenbach
authors.forename: David E
authors.initials: DE
authors.lastname: Swayne
authors.forename: Ruben
authors.initials: R
authors.lastname: Donis
authors.forename: Nancy
authors.initials: N
authors.lastname: Cox
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsuoka
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D000918:Antibody Specificity; D003429:Cross Reactions; D004196:Disease Outbreaks / Q000517:prevention & control; D005289:Ferrets; D006801:Humans; D053126:Influenza A Virus, H7N7 Subtype / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008958:Models, Molecular; D010641:Phenotype; D016865:Reassortant Viruses / Q000254:growth & development / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated