A randomized, controlled non-inferiority trial comparing A(H1N1)pmd09 vaccine antigen, with and without AS03 adjuvant system, co-administered or sequentially administered with an inactivated trivalent seasonal influenza vaccine

BMC Infect Dis. 2012 Oct 30:12:279. doi: 10.1186/1471-2334-12-279.

Abstract

Background: At the time of the influenza A(H1N1)pmd09 pandemic it was not known if concurrent or sequential administration of seasonal trivalent influenza vaccine (TIV) with pandemic vaccine was preferred.

Methods: Immunogenicity and safety were assessed in 871 healthy subjects aged 19-40 years who were randomised into six groups to receive co-administration or sequential administration of TIV and two doses of A(H1N1)pmd09 vaccine (either unadjuvanted or adjuvanted with AS03, an α-tocopherol and squalene-based oil-in-water emulsion).

Results: Safety and immunogenicity data (by haemagglutination inhibition [HI] assay) after each dose and six months post-Dose 1 are reported here. Co-administration of A(H1N1)pmd09 vaccine with TIV reduced the HI immune responses to A(H1N1)pmd09 vaccine. However, serologic responses with both co-administration and sequential schedules met the European and US regulatory criteria for pandemic and seasonal influenza vaccines up to six months following the first vaccine dose. The AS03-adjuvanted formulation elicited higher immune responses at all time points. Prior administration or co-administration of A(H1N1)pmd09 vaccine did not affect immune responses to TIV.

Conclusions: Co-administration of TIV and A(H1N1)pmd09 vaccine negatively influenced A(H1N1)pmd09 vaccine immunogenicity but had no effect on TIV responses. The non-adjuvanted and adjuvanted vaccines demonstrated strong immune responses against all vaccine strains for up to six months following the first vaccine dose.

Trial registration: ClinicalTrials.gov NCT00985673.

Publication types

  • 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*
  • Adjuvants, Immunologic / adverse effects
  • Adult
  • Antibodies, Viral / blood
  • Drug Combinations
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Female
  • Humans
  • 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*
  • Young Adult
  • alpha-Tocopherol / administration & dosage*
  • alpha-Tocopherol / adverse effects

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00985673