title: Comparative immunogenicity and cross-clade protective efficacy of mammalian cell-grown inactivated and live attenuated H5N1 reassortant vaccines in ferrets.
abstract: Continued H5N1 virus infection in humans highlights the need for vaccine strategies that provide cross-clade protection against this rapidly evolving virus. We report a comparative evaluation in ferrets of the immunogenicity and cross-protective efficacy of isogenic mammalian cell-grown, live attenuated influenza vaccine (LAIV) and adjuvanted, whole-virus, inactivated influenza vaccine (IIV), produced from a clade 1 H5N1 6:2 reassortant vaccine candidate (caVN1203-Len17rg) based on the cold-adapted A/Leningrad/134/17/57 (H2N2) master donor virus. Two doses of LAIV or IIV provided complete protection against lethal homologous H5N1 virus challenge and a reduction in virus shedding and disease severity after heterologous clade 2.2.1 H5N1 virus challenge and increased virus-specific serum and nasal wash antibody levels. Although both vaccines demonstrated cross-protective efficacy, LAIV induced higher levels of nasal wash IgA and reduction of heterologous virus shedding, compared with IIV. Thus, enhanced respiratory tract antibody responses elicited by LAIV were associated with improved cross-clade protection.
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Kortney M
authors.initials: KM
authors.lastname: Gustin
authors.forename: Taronna R
authors.initials: TR
authors.lastname: Maines
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Belser
authors.forename: Neal
authors.initials: N
authors.lastname: van Hoeven
authors.forename: Xuihua
authors.initials: X
authors.lastname: Lu
authors.forename: Libo
authors.initials: L
authors.lastname: Dong
authors.forename: Irina
authors.initials: I
authors.lastname: Isakova-Sivak
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Chen
authors.forename: J Theo M
authors.initials: JT
authors.lastname: Voeten
authors.forename: Jacco G M
authors.initials: JG
authors.lastname: Heldens
authors.forename: Han
authors.initials: H
authors.lastname: van den Bosch
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Klimov
authors.forename: Larisa
authors.initials: L
authors.lastname: Rudenko
authors.forename: Ruben O
authors.initials: RO
authors.lastname: Donis
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D056738:Cross Protection / Q000276:immunology*; D005289:Ferrets; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014776:Virus Cultivation / Q000379:methods; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic