title: A randomized trial of candidate inactivated quadrivalent influenza vaccine versus trivalent influenza vaccines in children aged 3-17 years.
abstract: BACKGROUND
  Two antigenically distinct influenza B lineages have cocirculated since 2001, yet trivalent influenza vaccines (TIVs) contain 1 influenza B antigen, meaning lineage mismatch with the vaccine is frequent. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages vs TIV in healthy children aged 3-17 years.
  
  
  METHODS
  Children were randomized 1:1:1 to receive QIV or 1 of 2 TIVs (either B/Victoria or B/Yamagata lineage; N = 2738). Hemagglutination-inhibition assays were performed 28 days after 1 or 2 doses in primed and unprimed children, respectively. Immunological noninferiority of QIV vs TIV against shared strains, and superiority against alternate-lineage B strains was based on geometric mean titers (GMTs) and seroconversion rates. Reactogenicity and safety were also assessed (Clinicaltrials.gov NCT01196988).
  
  
  RESULTS
  Noninferiority against shared strains and superiority against alternate-lineage B strains was demonstrated for QIV vs TIV. QIV was highly immunogenic; seroconversion rates were 91.4%, 72.3%, 70.0%, and 72.5% against A/H1N1, A/H3N2, B/Victoria, and B/Yamagata, respectively. Reactogenicity and safety of QIV was consistent with TIV.
  
  
  CONCLUSIONS
  QIV vs TIV showed superior immunogenicity for the additional B strain without interfering with immune responses to shared strains. QIV may offer improved protection against influenza B in children compared with current trivalent vaccines.
authors.affiliation: Department of Pediatrics, Golisano Children's Hospital, Upstate Medical University, Syracuse, New York 13210, USA. domachoj@upstate.edu
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Domachowske
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Pankow-Culot
authors.forename: Milagros
authors.initials: M
authors.lastname: Bautista
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.forename: Carine
authors.initials: C
authors.lastname: Claeys
authors.forename: Mathieu
authors.initials: M
authors.lastname: Peeters
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
authors.forename: Varsha
authors.initials: V
authors.lastname: Jain
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006679:HIV Seropositivity; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D008297:Male; D010679:Philippines; D012449:Safety; D014481:United States; D014611:Vaccination; D015164:Vaccines, Inactivated
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: noninferiority; pediatric; quadrivalent; seasonal influenza; superiority; trivalent