title: Impact of Adjuvants on the Immunogenicity and Efficacy of Split-Virion H7N9 Vaccine in Ferrets.
abstract: BACKGROUND
  An effective vaccine is urgently needed against the H7N9 avian influenza virus. We evaluated the immunogenicity and protective efficacy of a split-virion H7N9 vaccine with or without the oil-in-water adjuvants in ferrets.
  
  
  METHODS
  Ferrets were vaccinated with 2 doses of unadjuvanted, MF59 or AS03-adjuvanted A/Shanghai/2/2013 (H7N9) vaccine, and the induction of antibodies to hemagglutinin (HA) or neuraminidase proteins was evaluated. Ferrets were then challenged with wild-type H7N9 virus to assess the vaccine's protective efficacy. The vaccine composition and integrity was also evaluated in vitro.
  
  
  RESULTS
  Adjuvanted vaccines stimulated robust serum antibody titers against HA and neuraminidase compared with the unadjuvanted vaccines. Although there was a difference in adjuvanticity between AS03 and MF59 at a lower dose (3.75 µg of HA), both adjuvants induced comparable antibody responses after 2 doses of 15 µg. On challenge, ferrets that received adjuvanted vaccines showed lower viral burden than the control or unadjuvanted vaccine group. In vitro examinations revealed that the vaccine contained visible split-virus particles and retained the native conformation of HA recognizable by polyclonal and monoclonal antibodies.
  
  
  CONCLUSIONS
  The adjuvanted H7N9 vaccines demonstrated superior immunogenicity and protective efficacy against H7N9 infection in ferrets and hold potential as a vaccination regimen.
authors.affiliation: Department of Infectious Diseases.
authors.forename: Sook-San
authors.initials: SS
authors.lastname: Wong
authors.affiliation: Department of Infectious Diseases.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kaplan
authors.affiliation: Department of Infectious Diseases.
authors.forename: Mark
authors.initials: M
authors.lastname: Zanin
authors.affiliation: Department of Infectious Diseases.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Debeauchamp
authors.affiliation: Animal Resource Center.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kercher
authors.affiliation: Department of Infectious Diseases.
authors.forename: Jeri-Carol
authors.initials: JC
authors.lastname: Crumpton
authors.affiliation: Department of Infectious Diseases.
authors.forename: Patrick
authors.initials: P
authors.lastname: Seiler
authors.affiliation: Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Yilun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Infectious Diseases.
authors.forename: Scott
authors.initials: S
authors.lastname: Krauss
authors.affiliation: Department of Infectious Diseases.
authors.forename: Robert
authors.initials: R
authors.lastname: Webster
authors.affiliation: Department of Infectious Diseases.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D003429:Cross Reactions; D004306:Dose-Response Relationship, Immunologic; D004338:Drug Combinations; D005289:Ferrets; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D013185:Squalene / Q000008:administration & dosage / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol
keywords: H7N9; adjuvants; ferrets; influenza; vaccine