Immunogenicity and safety in adults of one dose of influenza A H1N1v 2009 vaccine formulated with and without AS03A-adjuvant: preliminary report of an observer-blind, randomised trial.

Governments and public health officials are preparing vaccination campaigns against the 2009 influenza A H1N1v pandemic strain. We evaluated two inactivated split-virion A/California/7/2009 H1N1v pandemic vaccines formulated with/without AS03(A), an oil-in-water emulsion adjuvant system containing tocopherol. This ongoing observer-blind study randomised 130 healthy adults aged 18-60 years to receive either AS03(A)-adjuvanted H1N1 vaccine containing 5.25 microg haemagglutinin (HA) (N=64) or non-adjuvanted H1N1 vaccine containing 21 microg HA (N=66) on Days 0 and 21. We performed a first analysis of reactogenicity and serum haemagglutination-inhibition (HI) antibody responses, 21 days after dose 1. Before vaccination, 12.5% in the AS03(A)-adjuvanted group and 13.1% in the non-adjuvanted group had vaccine-homologous HI titres >or=1:40. Immune responses were robust; HI seroconversion rates were 98.2% and 95.1% and HI seroprotection rates were 98.2% and 98.4%, respectively in the AS03(A) and non-adjuvanted groups. The vaccines were well tolerated with similar adverse event profiles. Solicited injection site and general symptoms were reported more frequently for AS03(A)-adjuvanted vaccine but these were transient and mainly mild to moderate in intensity. Based on accepted immunological surrogates, these preliminary data suggest that one dose of either AS03(A)-adjuvanted H1N1v vaccine at a reduced HA dose or non-adjuvanted H1N1v vaccine at a fourfold higher dose is sufficient to immunise healthy adults. The strong immune response is consistent with prevalent immunological priming but as this and the ability to mount immune response after vaccination may be modulated by age, further investigations in children and in the elderly as well as on the persistence of the immune response are warranted.