An observer-blind, randomized, multi-center trial assessing long-term safety and immunogenicity of AS03-adjuvanted or unadjuvanted H1N1/2009 influenza vaccines in children 10-17 years of age

Background: Vaccination is an effective strategy to prevent influenza. This observer-blind, randomized study in children 10-17 years of age assessed whether the hemagglutination inhibition (HI) antibody responses elicited by H1N1/2009 vaccines adjuvanted with AS03 (an adjuvant system containing alpha-tocopherol and squalene in an oil-in-water emulsion) or without adjuvant, met the European regulatory immunogenicity criteria at Days 21 and 182. Methods: Three hundred and ten healthy children were randomized (3:3:3:5) to receive one dose of 3.75 mu g hemagglutinin (HA) AS03(A)-adjuvanted vaccine, one or two doses of 1.9 mu g HA AS03(B)-adjuvanted vaccine, or one dose of 15 mu g HA pandemic vaccine. All children received a booster dose of the allocated vaccine at Day 182. Serum samples were tested for HI antibody response at Days 21, 42, 182 and 189. Results: All vaccination regimens elicited HI antibody responses that met the European regulatory criteria at Days 21 and 42. HI antibody responses fulfilling European regulatory criteria were still observed six months after the first vaccine dose in all study vaccines groups. Two doses of 1.9 mu g HA ASO3(B)-adjuvanted vaccine elicited the strongest HI antibody response throughout the study. The non-adjuvanted 15 mu g HA vaccine elicited a lower HI antibody response than the AS03-adjuvanted vaccines. At Day 189, the European regulatory criteria were met for all vaccines with baseline HI antibody titers as reference. An anamnestic response for all vaccines was suggested at Day 189, based on the rapid increase in HI antibody geometric mean titers (1.5-2.5-fold increase). Injection site reactogenicity was higher following the AS03-adjuvanted vaccines compared with the non-adjuvanted vaccine. No safety concerns were identified for any study vaccine. Conclusion: All study vaccines elicited HI antibody responses that persisted at purported protective levels through six months after vaccination and fulfilled the European regulatory criteria. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.