AS03B-adjuvanted H5N1 influenza vaccine in children 6 months through 17 years of age: a phase 2/3 randomized, placebo-controlled, observer-blinded trial

J Infect Dis. 2015 Mar 1;211(5):801-10. doi: 10.1093/infdis/jiu548. Epub 2014 Oct 6.

Abstract

Background: This phase 2/3, randomized, placebo-controlled, observer-blinded study assessed the immunogenicity, reactogenicity, and safety of an inactivated, split-virion H5N1 influenza vaccine (A/Indonesia/5/2005) in children aged 6 months through 17 years.

Methods: Children received 2 influenza vaccine doses 21 days apart, each containing 1.9 µg of hemagglutinin and AS03B adjuvant (5.93 mg of α-tocopherol). The randomization ratio was 8:3 for vaccine to placebo, with equal allocation between 3 age strata (6-35 months, 3-8 years, and 9-17 years). Immunogenicity against the vaccine strain was assessed 21 days after the first and second vaccine doses for all vaccinees, at day 182 for half, and at day 385 for the remaining half. Reactogenicity after each dose and safety up to 1 year after vaccination were evaluated.

Results: Within each age stratum, the lower limit of the 98.3% confidence interval for the day 42 seroprotection rate was ≥70%, thus fulfilling the US and European licensure criteria. The immune responses elicited by vaccine persisted well above baseline levels for 1 year. The vaccine was more reactogenic than placebo, but no major safety concerns were identified.

Conclusions: AS03B-adjuvanted H5N1 influenza vaccine was immunogenic and showed an acceptable safety profile in all age groups studied. Clinical Trials Registration: NCT01310413.

Keywords: AS03B; H5N1; Prepandrix™; adjuvant; influenza vaccine; pandemic.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adolescent
  • Antibodies, Viral / blood
  • Child
  • Child, Preschool
  • Drug Combinations
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Humans
  • Infant
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / adverse effects
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Male
  • Placebos / administration & dosage
  • Polysorbates / administration & dosage*
  • Polysorbates / adverse effects
  • Single-Blind Method
  • Squalene / administration & dosage*
  • Squalene / adverse effects
  • Treatment Outcome
  • Vaccination / methods
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / adverse effects
  • Vaccines, Inactivated / immunology
  • alpha-Tocopherol / administration & dosage*
  • alpha-Tocopherol / adverse effects

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Drug Combinations
  • Influenza Vaccines
  • Placebos
  • Polysorbates
  • Vaccines, Inactivated
  • Squalene
  • AS03 adjuvant
  • alpha-Tocopherol

Associated data

  • ClinicalTrials.gov/NCT01310413