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

Joanne M Langley,Louise Frenette,Ping Li,Scott Halperin,David Vaughn,Shelly Mcneil,Laurence Chu

doi:10.1186/1471-2334-12-279

Abstract

BackgroundAt 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.MethodsImmunogenicity 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).ResultsSafety 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.ConclusionsCo-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 registrationNCT00985673

Highlights

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
As the first wave of the A(H1N1)pmd09 pandemic passed, and the second wave began in the North American fall of that year, it was not known whether seasonal trivalent inactivated influenza vaccine (TIV) should be given before, after, or concurrently with the pandemic vaccine, or at all, during a pandemic year
Regulatory criteria for A(H1N1)pmd09 strain immunogenicity were met in all vaccine groups at 21 days after the first H1N1 dose and up to six months later, the Haemagglutination Inhibition (HI) antibody response against the pandemic strain following co-administration or sequential administration of TIV and A(H1N1)pmd09 vaccines was decreased compared to when A(H1N1)pmd09 vaccine was administered alone

Summary

Introduction

At the time of the influenza A(H1N1)pmd pandemic it was not known if concurrent or sequential administration of seasonal trivalent influenza vaccine (TIV) with pandemic vaccine was preferred. Results from a National Institute of Allergy and Infectious Diseases (NIAID) trial in 400 healthy adults published online in October 2009 suggested that coadministration of the two vaccines did not impair immune response to either vaccine [3], but otherwise there was little or no direct data on the immunogenicity and safety of co-administration of TIV and pandemic influenza vaccines to guide decision making. In addition to the potential safety and immunogenicity considerations of concurrent or sequential administration of TIV with a novel influenza vaccine antigen, it was not known if pandemic vaccines using an oil-inwater adjuvant would alter the immune response to TIV given before, concurrently, or after the pandemic vaccine. The World Health Organization (WHO) recommended production and use of oil-in water adjuvants (and live attenuated influenza vaccines), based on an anticipated limited vaccine availability on a global level [4]

Objectives

Methods

Results

Discussion

Conclusion