title: Effect of Previous-Year Vaccination on the Efficacy, Immunogenicity, and Safety of High-Dose Inactivated Influenza Vaccine in Older Adults.
abstract: BACKGROUND
  High-dose inactivated influenza vaccine (IIV-HD) is an alternative to the standard-dose inactivated influenza vaccine (IIV-SD) in the United States for influenza prevention in older adults. IIV-HD improved efficacy relative to IIV-SD in a randomized controlled trial. Recent observational studies suggest that previous influenza vaccination may influence the immunogenicity and effectiveness of current-season vaccination.
  
  
  METHODS
  The original study was a double-blind, randomized trial comparing IIV-HD to IIV-SD in adults aged ≥65 years over 2 influenza seasons. A subset of year 1 (Y1) participants reenrolled in year 2 (Y2), receiving vaccine by random assignment in both years. We evaluated the effect of Y1 vaccination on Y2 relative vaccine efficacy (VE), immunogenicity (hemagglutination inhibition [HAI] titers), and safety among reenrolled participants.
  
  
  RESULTS
  Of 14 500 Y1 participants, 7643 reenrolled in Y2. Relative to participants who received IIV-SD both seasons, VE was higher for IIV-HD vaccinees in Y2 (28.3% overall; 25.1% for Y1 IIV-HD, Y2 IIV-HD; and 31.6% for Y1 IIV-SD, Y2 IIV-HD). In multivariate logistic regression models, Y1 vaccine was not a significant modifier of Y2 VE (P= .43), whereas Y2 IIV-HD remained significantly associated with lower influenza risk (P= .043). Compared to administration of IIV-SD in both years, postvaccination HAI titers were significantly higher for patterns that included IIV-HD in Y2. No safety concerns were raised with IIV-HD revaccination.
  
  
  CONCLUSIONS
  IIV-HD is likely to provide clinical benefit over IIV-SD irrespective of previous-season vaccination with IIV-HD or IIV-SD. IIV-HD consistently improved immune responses, and no safety concerns emerged in the context of IIV-HD revaccination.
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: DiazGranados
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dunning
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania.
authors.forename: Corwin A
authors.initials: CA
authors.lastname: Robertson
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: H Keipp
authors.initials: HK
authors.lastname: Talbot
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania.
authors.forename: Victoria
authors.initials: V
authors.lastname: Landolfi
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania.|Department of Pediatrics, University of Pittsburgh School of Medicine, Pennsylvania.
authors.forename: David P
authors.initials: DP
authors.lastname: Greenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary; D000071497:Immunogenicity, Vaccine; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D016896:Treatment Outcome; D014481:United States
chemical_list: D007252:Influenza Vaccines
keywords: age 80 and older; aged; human influenza vaccines; inactivated vaccines; phase 3 clinical trial