title: A cell-based H7N1 split influenza virion vaccine confers protection in mouse and ferret challenge models.
abstract: BACKGROUND
  In recent years, several avian influenza subtypes (H5, H7 and H9) have transmitted directly from birds to man, posing a pandemic threat.
  
  
  OBJECTIVE
  We have investigated the immunogenicity and protective efficacy of a cell based candidate pandemic influenza H7 vaccine in pre-clinical animal models.
  
  
  METHODS
  Mice and ferrets were immunised with two doses of the split virus vaccine (12-24 microg haemagglutinin) with or without aluminium hydroxide adjuvant and challenged 3 weeks after second dose with the highly pathogenic A/chicken/Italy/13474/99 (H7N1) virus. The H7N1-specific serum antibody response was also measured. After challenge, viral shedding, weight loss, disease signs and death (only mice) were recorded.
  
  
  RESULTS
  Low-to-modest serum antibody titres were detected after vaccination. Nevertheless, the vaccine induced significant protection from disease after challenge with the wild-type virus. In the murine lethal challenge model, vaccination effectively prevented death and, furthermore, formulation with adjuvant reduced excessive weight loss and viral shedding. In ferrets, vaccination reduced viral shedding and protected against systemic spread of the virus.
  
  
  CONCLUSIONS
  We have extended to the H7 subtype the finding that protective efficacy may not be directly correlated with the pre-challenge levels of serum antibodies, a finding which could be of great importance in assessing the potential effectiveness of pandemic influenza vaccines.
authors.affiliation: Influenza Centre, The Gade Institute, University of Bergen, Bergen, Norway. rebecca.cox@gades.uib.no
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cox
authors.forename: Diane
authors.initials: D
authors.lastname: Major
authors.forename: Solveig
authors.initials: S
authors.lastname: Hauge
authors.forename: Abdullah S
authors.initials: AS
authors.lastname: Madhun
authors.forename: Karl A
authors.initials: KA
authors.lastname: Brokstad
authors.forename: Mirjam
authors.initials: M
authors.lastname: Kuhne
authors.forename: Jon
authors.initials: J
authors.lastname: Smith
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Vogel
authors.forename: Maria
authors.initials: M
authors.lastname: Zambon
authors.forename: Lars R
authors.initials: LR
authors.lastname: Haaheim
authors.forename: John
authors.initials: J
authors.lastname: Wood
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology* / Q000302:isolation & purification; D001835:Body Weight; D002642:Chick Embryo; D005260:Female; D005289:Ferrets; D007117:Immunization, Secondary; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007558:Italy; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D012720:Severity of Illness Index; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000276:immunology; D014771:Virion / Q000276:immunology / Q000302:isolation & purification; D017201:Virus Shedding
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007252:Influenza Vaccines; D022223:Vaccines, Subunit; D000536:Aluminum Hydroxide