Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus.
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.
Kobinger
Gary P
GP
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. gary_kobinger@phac-aspc.gc.ca
Meunier
Isabelle
I
Patel
Ami
A
Pillet
Stéphane
S
Gren
Jason
J
Stebner
Shane
S
Leung
Anders
A
Neufeld
James L
JL
Kobasa
Darwyn
D
von Messling
Veronika
V
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
D000914:Antibodies, Viral; D016207:Cytokines; D007252:Influenza Vaccines; D015850:Interleukin-6; D012333:RNA, Messenger