title: Immunogenicity and Safety of an Inactivated Quadrivalent Influenza Vaccine in US Children 6-35 Months of Age During 2013-2014: Results From A Phase II Randomized Trial.
abstract: BACKGROUND
  Viruses from 2 influenza B lineages co-circulate, leading to suboptimal protection with trivalent influenza vaccines (TIV). Quadrivalent influenza vaccines (QIV) containing both lineages offer broader protection.
  
  
  METHODS
  We compared inactivated seasonal QIV versus TIV (15 and 7.5 μg hemagglutinin [HA] for each influenza strain, respectively) in a phase II randomized (1 : 1), observer-blind trial in US children 6-35 months of age (identifier NCT01974895). The primary objective was to evaluate immune responses induced by QIV for the 4 vaccine strains 28 days after completion of vaccination. A secondary objective was to demonstrate superiority of QIV versus TIV for the B/Victoria strain contained in QIV but not TIV. Immunogenicity was evaluated in the per-protocol cohort (N = 280), and safety was evaluated in the intent-to-treat cohort (N = 314).
  
  
  RESULTS
  Seroconversion rates (SCRs) for QIV were 80.4% (95% confidence interval [CI], 73.0%-86.6%), 72.0% (95% CI, 63.9%-79.2%), 86.0% (95% CI, 79.2%-91.2%), and 66.4% (95% CI, 58.1%-74.1%) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria, respectively. Quadrivalent influenza vaccines demonstrated immunogenic superiority over TIV for B/Victoria with a geometric mean titer ratio of 4.73 (95% CI, 3.73%-5.99%) and SCR difference of 54.02% (95% CI, 43.88%-62.87%). Safety was similar between the vaccine groups despite the QIV's higher antigen content. No serious adverse events were reported related to vaccination.
  
  
  CONCLUSIONS
  Quadrivalent influenza vaccine (15 µg HA/strain) was immunogenic with an acceptable safety profile. The next phase of its development in children 6-35 months of age is a phase III trial in countries where it is not yet licensed. In countries where it is already licensed, a switch from TIV to QIV would provide broader protection in this vulnerable group.
authors.affiliation: GSK Vaccines, Vaccine Discovery and Development, King of Prussia, Pennsylvania.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: GSK Vaccines, Biostatistics, King of Prussia, Pennsylvania.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Chandrasekaran
authors.affiliation: SUNY Upstate Medical Center, Syracuse, New York.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Domachowske
authors.affiliation: GSK Vaccines, Biostatistics, King of Prussia, Pennsylvania.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: GSK Vaccines, Vaccine Discovery and Development, King of Prussia, Pennsylvania.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
authors.affiliation: GSK Vaccines, Vaccine Discovery and Development, King of Prussia, Pennsylvania.
authors.forename: Varsha K
authors.initials: VK
authors.lastname: Jain
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D002675:Child, Preschool; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D000071497:Immunogenicity, Vaccine; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D009981:Influenza B virus; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D016037:Single-Blind Method; D015164:Vaccines, Inactivated / Q000627:therapeutic use
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: children; immunogenicity; influenza; quadrivalent; vaccine