Immunological priming induced by a two-dose series of H5N1 influenza antigen, administered alone or in combination with two different formulations of AS03 adjuvant in adults: results of a randomised single heterologous booster dose study at 15 months.

One influenza pandemic preparedness strategy involves priming a population with a pre-pandemic subtype-specific vaccine and boosting the immunological response at the time of the pandemic with a strain-matched vaccine. In the current study, adults (n=469) randomised 15 months previously to receive an A/Indonesia/5/2005 (H5N1) influenza vaccine (3.75 μg haemagglutinin antigen [HA]) administered alone or in combination with an oil-in-water emulsion based Adjuvant System containing 11.86 mg (AS03(A)) or 5.93 mg (AS03(B)) tocopherol per dose, received one booster dose of A/turkey/Turkey/1/2005 (H5N1) vaccine (3.75 μg HA) with or without AS03(A). An anamnestic antibody response that met US regulatory acceptance criteria was observed 15 months after priming. Although superior immunogenicity of AS03-adjuvanted compared to unadjuvanted priming was not demonstrated, higher antibody titres which persisted longer were seen when both priming and boosting regimens were adjuvanted. This may affect duration of response or heterologous immunity. The booster vaccines had a clinically acceptable safety/reactogenicity profile after adjuvanted or unadjuvanted priming. This study has been registered at www.clinicaltrials.gov NCT00771615.

RCT Entities:   Population Interventions Outcomes