title: Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus.
abstract: BACKGROUND
  The emergence and global spread of the pandemic H1N1 2009 influenza virus have raised questions regarding the protective effect of available seasonal vaccines and the efficacy of a newly produced matched vaccine.
  
  
  METHODS
  Ferrets were immunized with the 2008-2009 formulations of commercially available live attenuated (FluMist; MedImmune) or split-inactivated (Fluviral; GlaxoSmithKline) vaccines, a commercial swine vaccine (FluSure; Pfizer), or a laboratory-produced matched inactivated whole-virus vaccine (A/Mexico/InDRE4487/2009). Adaptive immune responses were monitored, and the animals were challenged with A/Mexico/InDRE4487/2009 after 5 weeks.
  
  
  RESULTS
  Only animals that received the swine or matched vaccines developed detectable hemagglutination-inhibiting antibodies against the challenge virus, whereas a T cell response was exclusively detected in animals vaccinated with FluMist. After challenge, all animals had high levels of virus replication in the upper respiratory tract. However, preexisting anti-pandemic H1N1 2009 antibodies resulted in reduced clinical signs and improved survival. Surprisingly, FluMist was associated with a slight increase in mortality and greater lung damage, which correlated with early up-regulation of interleukin-10.
  
  
  CONCLUSIONS
  The present study demonstrates that a single dose of matched inactivated vaccine confers partial protection against a pandemic H1N1 2009 virus, and it suggests that a higher dose or prime-boost regimen may be required. The consequences of mismatched immunity to influenza merit further investigation.
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. gary_kobinger@phac-aspc.gc.ca
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meunier
authors.forename: Ami
authors.initials: A
authors.lastname: Patel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pillet
authors.forename: Jason
authors.initials: J
authors.lastname: Gren
authors.forename: Shane
authors.initials: S
authors.lastname: Stebner
authors.forename: Anders
authors.initials: A
authors.lastname: Leung
authors.forename: James L
authors.initials: JL
authors.lastname: Neufeld
authors.forename: Darwyn
authors.initials: D
authors.lastname: Kobasa
authors.forename: Veronika
authors.initials: V
authors.lastname: von Messling
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001831:Body Temperature; D001835:Body Weight; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005289:Ferrets; D006384:Hemagglutination / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D015850:Interleukin-6 / Q000032:analysis; D008168:Lung / Q000473:pathology; D009296:Nasal Cavity / Q000737:chemistry; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007252:Influenza Vaccines; D015850:Interleukin-6; D012333:RNA, Messenger