title: High-dose trivalent influenza vaccine compared to standard dose vaccine in elderly adults: safety, immunogenicity and relative efficacy during the 2009-2010 season.
abstract: BACKGROUND
  High-dose trivalent influenza vaccine was developed to improve antibody responses to influenza vaccine in the elderly and hence potentially impact favorably on influenza-associated morbidity and mortality in this population.
  
  
  METHODS
  A phase IIIb, multicenter, randomized, double-blind, controlled trial was conducted to compare High-Dose (HD) trivalent inactivated influenza vaccine (60μg of hemagglutinin [HA] per strain) to standard dose (SD) vaccine (15μg of HA per strain) in adults ≥65 years of age. Assessments of safety (serious adverse events [SAE]), immunogenicity (hemagglutination inhibition [HAI] titers) and relative efficacy were performed during the 2009-2010 influenza season, which coincided with the H1N1 pandemic.
  
  
  RESULTS
  A total of 9172 participants were enrolled in 99 research centers in the US (6117 and 3055 randomized to the HD and SD groups, respectively). Within 180 days after vaccination, 6.7% and 6.5% of participants in the HD and SD vaccine groups, respectively, experienced at least one SAE, of which 0.4% and 0.3% had a fatal outcome. A total of 0.5% of participants in both groups discontinued the study due to a SAE. Post-vaccination HAI titers and rate of post-vaccination HAI titer ≥1:40 were significantly higher in the HD group. No cases of influenza caused by viral types/subtypes similar to those in the vaccines were observed. All cases genetically or antigenically characterized were classified as similar to influenza A/California/7/2009 (H1N1), the pandemic strain. The vaccine efficacy of HD vaccine relative to SD vaccine against any influenza viral type/subtype was 12.6% (95% CI -140.5; 65.8) in the intent-to-treat analysis.
  
  
  CONCLUSIONS
  High-dose trivalent inactivated influenza vaccine is safe and well tolerated and provides superior immune responses compared to standard dose vaccine. Demonstration of a superior vaccine efficacy requires a separate large randomized, controlled trial.
authors.affiliation: Sanofi Pasteur, 1 Discovery Drive, Swiftwater, PA 18370, USA. carlos.diazgranados@sanofipasteur.com
authors.forename: Carlos A
authors.initials: CA
authors.lastname: DiazGranados
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dunning
authors.forename: Emilia
authors.initials: E
authors.lastname: Jordanov
authors.forename: Victoria
authors.initials: V
authors.lastname: Landolfi
authors.forename: Martine
authors.initials: M
authors.lastname: Denis
authors.forename: H Keipp
authors.initials: HK
authors.lastname: Talbot
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D014481:United States
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines