Immunogenicity, reactogenicity, and safety of inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine in healthy adults aged ≥18 years: a phase III, randomized trial

Vaccine. 2014 Mar 14;32(13):1480-7. doi: 10.1016/j.vaccine.2014.01.022. Epub 2014 Jan 28.


Background: Two influenza B lineages have been co-circulating since the 1980s, and because inactivated trivalent influenza vaccine (TIV) contains only one B strain, it provides little/no protection against the alternate B-lineage. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in healthy adults.

Methods: Subjects received one dose of QIV (lot 1, 2, or 3) or one of two TIVs (B strain from Victoria or Yamagata lineage); randomization was 2:2:2:1:1. Hemagglutination-inhibition assays were performed 21-days post-vaccination; superiority of QIV versus TIV for the alternate B-lineage was demonstrated if the 95% confidence interval (CI) lower limit for the GMT ratio was ≥1.5, and non-inferiority against the shared strains was demonstrated if the 95% CI upper limit for the GMT ratio was ≤1.5. Reactogenicity and safety were assessed during the post-vaccination period. NCT01196975.

Results: Immunogenicity of QIV lots was consistent, QIV was superior to TIV for the alternate B-lineage strain, and QIV was non-inferior versus TIVs for shared strains (A/H1N1, A/H3N2, B-strain). Reactogenicity and safety profile of the QIV was consistent with seasonal influenza vaccines.

Conclusion: QIV provided superior immunogenicity for the added B strain without affecting the antibody response to the TIV strains, and without compromising safety.

Keywords: Inactivated quadrivalent influenza vaccine; Seasonal influenza; Victoria lineage; Yamagata lineage.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood
  • Antibody Formation
  • Double-Blind Method
  • Female
  • Hemagglutination Inhibition Tests
  • Humans
  • Influenza A Virus, H1N1 Subtype
  • Influenza A Virus, H3N2 Subtype
  • Influenza B virus*
  • Influenza Vaccines / classification
  • Influenza Vaccines / therapeutic use*
  • Influenza, Human / prevention & control*
  • Male
  • Middle Aged
  • Vaccines, Inactivated / therapeutic use
  • Young Adult


  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Inactivated

Associated data