A randomized trial of candidate inactivated quadrivalent influenza vaccine versus trivalent influenza vaccines in children aged 3-17 years

J Infect Dis. 2013 Jun 15;207(12):1878-87. doi: 10.1093/infdis/jit091. Epub 2013 Mar 7.

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.

Keywords: noninferiority; pediatric; quadrivalent; seasonal influenza; superiority; trivalent.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Double-Blind Method
  • Europe
  • Female
  • HIV Seropositivity
  • Hemagglutination Inhibition Tests
  • Humans
  • Infant
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A virus / immunology*
  • Influenza B virus / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Male
  • Philippines
  • Safety
  • United States
  • Vaccination
  • Vaccines, Inactivated

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Inactivated

Associated data

  • ClinicalTrials.gov/NCT01196988