Long-term immunogenicity of an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine in young and elderly adults: an observer-blind, randomized trial.

ABSTRACT

BACKGROUND: This study (NCT00979602) evaluated the immunogenicity and relative protective efficacy of one dose of influenza A(H1N1)pdm09 vaccine with or without AS03 (an α-tocopherol oil-in-water emulsion based Adjuvant System). METHODS: Four thousands and forty-eight healthy adults aged ≥ 18 years were randomized (11) to receive one dose of either the adjuvanted split virion (3.75 µg hemagglutinin antigen [HA]/AS03) or non-adjuvanted (15 µg HA) vaccine. Hemagglutination inhibition [HI] antibody response was evaluated before vaccination and at Days 21, 42 and 182 (Month 6). Safety of the study vaccines was evaluated during the entire study duration. RESULTS: At Day 21, both study vaccines induced HI immune responses meeting the US regulatory criteria in subjects 18-64 years (seroprotection rate [SPR] 98.0% [97.1-98.6]; seroconversion rate [SCR] 89.7% [88.0-91.2] in the AS03-adjuvanted group; SPR 91.4% [89.9-92.8]; SCR 74.6% [72.3-76.9] in the non-adjuvanted group) and >64 years of age (SPR 86.0% [82.5-89.0]; SCR 75.3% [71.1-79.2] in the AS03-adjuvanted group; SPR 69.1% [64.6-73.3]; SCR 56.7% [52.0-61.3] in the non-adjuvanted group). The AS03-adjuvanted vaccine induced higher HI geometric mean titers than the non-adjuvanted vaccine at all time points. At Month 6, only subjects 18-64 years of age from both vaccine groups still met the US regulatory criteria (SPR 82.1% [80.0-84.1]; SCR 62.3% [59.6-64.8] in the AS03-adjuvanted group; SPR 75.3% [72.9-77.5]; SCR 53.7% [51.0-56.4] in the non-adjuvanted group). Protective efficacy was not evaluated due to low number of RT-qPCR-confirmed A(H1N1)pdm09 influenza cases. Through Month 12, 216 serious adverse events (in 157 subjects: 84 in the AS03-adjuvanted and 73 in the non-adjuvanted group) and 12 potentially immune mediated diseases (5 in the AS03-adjuvanted and 7 in the non-adjuvanted group) were reported. CONCLUSION: A single dose of either adjuvanted or non-adjuvanted influenza A(H1N1)pdm09 vaccine induced protective HI antibody levels against the A/California/7/2009 strain that persisted through Month 6 in the 18-64 years population.