Safety and Immunogenicity of Cell Culture-Derived A/H3N2 Variant Influenza Vaccines: A Phase I Randomized, Observer-Blind, Dose-Ranging Study

J Infect Dis. 2015 Jul 1;212(1):72-80. doi: 10.1093/infdis/jiu826. Epub 2014 Dec 23.


Background: A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important.

Methods: In this phase I, randomized, observer-blind, dose-ranging study, 627 healthy subjects ≥ 3 years of age were randomized to receive 2 vaccinations with H3N2c cell-culture-derived vaccine doses containing 3.75 µg, 7.5 µg, or 15 µg hemagglutinin antigen of H3N2v with or without MF59 (registered trademark of Novartis AG) adjuvant (an oil-in-water emulsion). This paper reports Day 43 planned interim data.

Results: Single MF59-adjuvanted H3N2c doses elicited immune responses in almost all subjects regardless of antigen and adjuvant dose; the Center for Biologics Evaluation Research and Review (CBER) licensure criteria were met for all groups. Subjects with prevaccination hemagglutination inhibition titers <10 and children 3-<9 years achieve CBER criteria only after receiving 2 doses of nonadjuvanted H3N2c vaccine. Highest antibody titers were observed in the 7.5 µg + 0.25 mL MF59 groups in all age cohorts. MF59-adjuvanted H3N2c vaccines showed the highest rates of solicited local and systemic events, predominately mild or moderate.

Conclusions: A single dose of H3N2c vaccine may be immunogenic and supports further development of MF59-adjuvanted H3N2c vaccines, especially for pediatric populations.

Clinical trials registration: identifier NCT01855945 (

Keywords: A/H3N2 variant; cell culture–derived; immunogenicity; influenza; safety; vaccine; virus.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood
  • Cell Culture Techniques
  • Child
  • Child, Preschool
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Humans
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Influenza A Virus, H3N2 Subtype / isolation & purification
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects*
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / isolation & purification
  • Influenza, Human / prevention & control*
  • Male
  • Middle Aged
  • Polysorbates / administration & dosage
  • Polysorbates / adverse effects
  • Single-Blind Method
  • Squalene / administration & dosage
  • Squalene / adverse effects
  • Technology, Pharmaceutical / methods*
  • Young Adult


  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Influenza Vaccines
  • MF59 oil emulsion
  • Polysorbates
  • Squalene

Associated data