Safety and immunogenicity of an MF59®-adjuvanted A/H1N1 pandemic influenza vaccine in children from three to seventeen years of age

Abstract

ObjectivesThis study was designed to identify the optimal dose of an MF59®-adjuvanted, monovalent, A/H1N1 influenza vaccine in healthy paediatric subjects. MethodsSubjects aged 3–8 years (n=194) and 9–17 years (n=160) were randomized to receive two primary doses of A/H1N1 vaccine containing either 3.75μg antigen with half a standard dose of MF59 adjuvant, 7.5μg antigen with a full dose of MF59, or (children 3–8 years only), a non-adjuvanted 15μg formulation. A booster dose of MF59-adjuvanted seasonal influenza vaccine including homologous A/H1N1 strain was given one year after priming. Immunogenicity was assessed by haemagglutination inhibition (HI) and microneutralization assays. Vaccine safety was assessed throughout the study (up to 18 months). ResultsA single priming dose of either MF59-adjuvanted formulation was sufficient to meet the European licensure criteria for pandemic influenza vaccines (HI titres ≥1:40>70%; seroconversion>40%; and GMR>2.5). Two non-adjuvanted vaccine doses were required to meet the same licensure criteria. After first and second doses, percentage of subjects with HI titres ≥1:40 were between 97% and 100% in the adjuvanted vaccine groups compared with 68% and 91% in the non-adjuvanted group, respectively. Postvaccination seroconversion rates ranged from 91% to 98% in adjuvanted groups and were 68% (first dose) and 98% (second dose) in the non-adjuvanted group. HI titres ≥1:330 after primary doses were achieved in 69% to 90% in adjuvanted groups compared with 41% in the non-adjuvanted group. Long-term antibody persistence after priming and a robust antibody response to booster immunization were observed in all vaccination groups. All A/H1N1 vaccine formulations were generally well tolerated. No vaccine-related serious adverse events occurred, and no subjects were withdrawn from the study due to an adverse event. ConclusionsAn MF59-adjuvanted influenza vaccine containing 3.75μg of A/H1N1 antigen was well tolerated and sufficiently immunogenic to meet all the European licensure criteria after a single dose in healthy children 3–17 years old.