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

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.

Figure 1

Study design. Total vaccinated cohort (TVC): all subjects with at least one documented vaccine dose with available immunogenicity results. According-to-protocol (ATP) cohort for immunogenicity: all evaluable subjects (i.e., those meeting all eligibility criteria, with no elimination criteria during the relevant analysis interval), who received two vaccine doses and for whom assay results were available at Day 42.

Figure 2

Incidence and 95%CI of solicited local and general symptoms recorded during the 7-day post-vaccination follow-up period (Total vaccinated cohort). Group definitions: Group A: TIV+Placebo (Day 0); 15 μg (Day 21); 15 μg (Day 42); Group B: TIV+Placebo (Day 0); 3.75 μg/AS03 (Day 21); 3.75 μg/AS03 (Day 42); Group C: 15 μg+TIV (Day 0); 15 μg (Day 21); Placebo (Day 42); Group D: 3.75 μg/AS03+TIV (Day 0); 3.75 μg/AS03 (Day 21); Placebo (Day 42); Group E: 15 μg+Placebo (Day 0); 15 μg (Day 21); TIV (Day 42); Group F: 3.75 μg/AS03+Placebo (Day 0); 3.75 μg/AS03 (Day 21); TIV (Day 42).