title: Safety and immunogenicity of high-dose trivalent inactivated influenza vaccine in adults 50-64 years of age.
abstract: BACKGROUND
  Individuals 50-64 years of age have reduced immune responses to influenza vaccines. The current study examined whether a high-dose inactivated trivalent influenza vaccine (IIV3-HD) might improve immune responses over a standard-dose inactivated influenza vaccine (IIV3-SD) in this age group.
  
  
  METHODS
  This was a multicenter, observer-blinded, randomized, active-controlled phase II trial. Adults 50-64 years of age were randomized 1:1 to receive IIV3-HD or IIV3-SD. Hemagglutination inhibition titers were measured before and 28 days after vaccination. Reactogenicity was recorded for 7 days after vaccination and adverse events for 28 days.
  
  
  RESULTS
  148 participants received IIV3-HD and 152 received IIV3-SD. For all vaccine strains, day 28 geometric mean hemagglutination inhibition titers were significantly higher in the IIV3-HD group than in the IIV3-SD group (geometric mean titer ratio [95% confidence interval (CI)]=1.43 [1.04-1.97] for A/H1N1, 1.65 [1.21-2.25] for A/H3N2, and 1.60 [1.23-2.08] for B). Seroconversion rates were significantly higher in the IIV3-HD group than in the IIV3-SD group for strains A/H3N2 and B but not A/H1N1 (difference [95% CI]=13.5% [4.76-22.0] for A/H3N2, 23.1% [11.7-33.6] for B, and -0.2% [-9.66 to 9.18] for A/H1N1). The post-vaccination seroprotection rate was significantly higher in the IIV3-HD group than in the IIV3-SD group for strain B but not for strains A/H1N1 or A/H3N2 (difference=9.1% [2.95-15.7] for B, 2.0% [-0.907 to 5.68] for A/H1N1, and 0.6% [-3.14 to 4.43] for A/H3N2). Reactogenicity was higher in the IIV3-HD group than in the IIV3-SD group, but reactions were mostly of low intensity, transient, and self-limited. Rates of unsolicited adverse events were similar between groups. No serious AEs, AEs leading to early withdrawal, or deaths were reported.
  
  
  CONCLUSIONS
  The study suggests that in adults 50-64 years of age, IIV3-HD may improve immunogenicity compared to IIV3-SD while maintaining an acceptable safety profile.
authors.affiliation: Sanofi Pasteur, Inc., Swiftwater, PA, USA. Electronic address: carlos.diazgranados@sanofipasteur.com.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: DiazGranados
authors.affiliation: Columbia Medical Practice, Columbia, MD, USA.
authors.forename: William
authors.initials: W
authors.lastname: Saway
authors.affiliation: Infectious Disease Specialists, PC, Missoula, MT, USA.
authors.forename: James
authors.initials: J
authors.lastname: Gouaux
authors.affiliation: Rapid Medical Research, Inc., Beachwood, OH, USA.
authors.forename: Mira
authors.initials: M
authors.lastname: Baron
authors.affiliation: Women's Healthcare Associates and Rosemark Women Care Specialists, Idaho Falls, ID, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Baker
authors.affiliation: Sanofi Pasteur, SA, Lyon, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Denis
authors.affiliation: Sanofi Pasteur, Inc., Swiftwater, PA, USA.
authors.forename: Emilia
authors.initials: E
authors.lastname: Jordanov
authors.affiliation: Sanofi Pasteur, Inc., Swiftwater, PA, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Landolfi
authors.affiliation: Sanofi Pasteur Ltd, Toronto, Canada.
authors.forename: Eddy
authors.initials: E
authors.lastname: Yau
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D016896:Treatment Outcome; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: Clinical trial; Inactivated; Influenza vaccines; Middle aged; Phase II; Safety