Immunogenicity, safety, and tolerability of two trivalent subunit inactivated influenza vaccines: a phase III, observer-blind, randomized, controlled multicenter study

Viral Immunol. 2012 Jun;25(3):216-25. doi: 10.1089/vim.2011.0063.


The objective of this study was to evaluate and compare the immunogenicity, safety, and tolerability of two influenza subunit vaccines, a primarily European-marketed trivalent vaccine (Agrippal®, Novartis Vaccines), and a predominantly U.S.-marketed control trivalent vaccine (Fluvirin®, Novartis Vaccines), in subjects aged 3-64 y. The immunogenicity of both vaccines was evaluated according to the Center for Biologics Evaluation and Research (CBER) criteria. This clinical trial was performed between April and December 2007 in Argentina. A total of 1893 subjects were stratified into three age groups (3-8 y, 9-17 y, and 18-64 y), and randomized in a 2:1 ratio to receive either Agrippal or Fluvirin. Adolescents and adults received one dose of vaccine intramuscularly, whereas children aged 3-8 years received two vaccine doses, administered 4 wk apart. Antibody levels were measured by means of hemagglutination inhibition assay before vaccination (baseline); 21 d after the first vaccination (adults and adolescents); and, for children aged 3-8 y, 28 d after the first vaccination and 21 d after the second vaccine dose. Adverse reactions were solicited via diary cards for 7 d after each vaccination, and unsolicited adverse events were reported throughout the study period. Both vaccines were safe and well-tolerated, and elicited robust immunogenic responses in all age groups, meeting both CBER licensure criteria for all three viral strains after completion of the age-recommended vaccination schedule. These findings support the use of the trivalent subunit influenza vaccines Agrippal and Fluvirin for universal vaccination campaigns on an annual basis. NCT00464672.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • Argentina
  • Child
  • Child, Preschool
  • Female
  • Hemagglutination Inhibition Tests
  • Humans
  • Influenza Vaccines* / administration & dosage
  • Influenza Vaccines* / adverse effects
  • Influenza Vaccines* / immunology
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control*
  • Male
  • Middle Aged
  • Treatment Outcome
  • Vaccination
  • Vaccines, Inactivated* / administration & dosage
  • Vaccines, Inactivated* / adverse effects
  • Vaccines, Inactivated* / immunology
  • Vaccines, Subunit* / administration & dosage
  • Vaccines, Subunit* / immunology
  • Young Adult


  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Inactivated
  • Vaccines, Subunit

Associated data