Open-label, randomised, parallelgroup, multicentre study to evaluate the safety, tolerability and immunogenicity of an AS03_B/oil-inwater emulsion-adjuvanted (AS03_B) split-virion versus non-adjuvanted whole-virion H1N1 influenza vaccine in UK children 6 months to 12 years of age

Objective: To evaluate the safety, tolerability and immunogenicity of an AS03_B/oil-in-water emulsionadjuvanted (AS03_B) split-virion versus non-adjuvanted whole-virion H1N1 influenza vaccine in UK children aged 6 months to 12 years. Design: Multicentre, randomised, head-to-head, open-label trial. Setting: Five UK sites (Oxford, Bristol, Southampton, Exeter and London). Participants: Children aged 6 months to < 13 years, for whom a parent or guardian had provided written informed consent and who were able to comply with study procedures, were eligible for inclusion. Interventions: A tocopherol/oil-in-water emulsionadjuvanted (AS03_B) egg culture-derived split-virion H1N1 vaccine and a non-adjuvanted cell culturederived whole-virion vaccine, given as a two-dose schedule, 21 days apart, were compared. Participants were grouped into those aged 6 months to < 3 years (younger group) and 3 years to < 13 years of age (older group) and were randomised by study investigators (1: 1 ratio) to receive one of the two vaccines. Vaccines were administered by intramuscular injection (deltoid or anterior-lateral thigh, depending on age and muscle bulk). Local reactions and systemic symptoms were collected for 1 week post immunisation, and serum was collected at baseline and after the second dose. To assess safety and tolerability, parents or guardians recorded the following information in diary cards from days 0-7 post vaccination: axillary temperature, injection site reactions, solicited and unsolicited systemic symptoms, and medications. Main outcome measure: Comparison between vaccines of the percentage of participants demonstrating seroconversion by microneutralisation assay. Results: Among 937 children receiving vaccine, perprotocol seroconversion rates were higher after the AS03B-adjuvanted vaccine than after the whole-virion vaccine (98.2% vs 80.1% in children < 3 years, 99.1% vs 95.9% among those aged 3-12 years), as were severe local reactions (3.6% vs 0.0% in those under 5 years, 7.8% vs 1.1% in those aged 5-12 years), irritability in children < 5 years (46.7% vs 32.0%), and muscle pain in older children (28.9% vs 13.2%). The second dose of the adjuvanted vaccine was more reactogenic than the first, especially for fever > 38.0°C in those under 5 years of age (8.9% vs 22.4%). Conclusion: The adjuvanted vaccine, although reactogenic, was more immunogenic, especially in younger children, indicating the potential for improved immunogenicity of influenza vaccines in this age group. Trial registration number: ISRCTN89141709.