Enhanced immunogenicity of seasonal influenza vaccines in young children using MF59 adjuvant

Pediatr Infect Dis J. 2009 Jul;28(7):563-71. doi: 10.1097/INF.0b013e31819d6394.


Background: Children have high morbidity and hospitalization rates from seasonal influenza. Meta-analyses suggest that conventional inactivated influenza vaccines are of low efficacy in young children, making vaccines that induce greater and broader immune protection in this vulnerable population a medical priority. Adjuvanted influenza vaccines may offer a solution.

Subjects and methods: Unprimed healthy children (6 to <36 months) were enrolled in an observer-blinded study and randomly assigned to receive 2 doses of MF59-adjuvanted vaccine (Sub/MF59, n = 130) or nonadjuvanted split vaccine (split, n = 139); subgroups of these (n = 43 and 46, respectively) received a booster dose 1 year later. Safety and clinical tolerability were assessed after each dose. Hemagglutination inhibition antibody titers were measured against influenza A and B strains included in the formulation of the vaccines and against mismatched strains.

Results: Clinical tolerability and safety were generally comparable between vaccine groups, though some transient, mild solicited reactions were more frequent in the Sub/MF59 group. Postvaccination hemagglutination inhibition antibody titers to all 3 vaccine strains were significantly higher with Sub/MF59 than with split vaccine (all comparisons P < 0.001) after each of the 3 vaccine doses. In addition, Sub/MF59 induced significantly higher cross-reactivity against A/H3N2 and A/H1N1 mismatched strains.

Conclusion: MF59-adjuvanted influenza vaccine was well tolerated in healthy young children after each of 3 doses and induced greater, longer-lasting, and broader immune responses than a nonadjuvanted split vaccine. The enhanced immunogenicity of the adjuvanted vaccine was most evident in very young children and for the B vaccine strain.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / adverse effects
  • Antibodies, Viral / blood
  • Child, Preschool
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunization, Secondary / methods
  • Infant
  • Influenza A virus / immunology
  • Influenza B virus / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*
  • Male
  • Polysorbates / administration & dosage*
  • Polysorbates / adverse effects
  • Squalene / administration & dosage*
  • Squalene / adverse effects
  • Vaccination / methods


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