Safety and immunogenicity of a split-virion AS03A-adjuvanted A/Indonesia/05/2005 (H5N1) vaccine in Taiwanese adults.

This study evaluated the immune response elicited by two formulations of an AS03(A)-adjuvanted H5N1 A/Indonesia/05/2005 prepandemic influenza vaccine, developed using manufacturing processes with or without thiomersal. In addition, it also evaluated compliance to the Centre for Biologics Evaluation and Research and Committee for Medicinal Products for Human Use (CHMP) immunogenicity guidance criteria for pandemic influenza vaccines in adults. This phase III, observer-blind, randomized study (NCT00812981) enrolled 320 subjects aged 18-60 years into two groups to receive, 21 days apart, two doses of the formulation manufactured using either the thiomersal-containing process (Group TC) or the thiomersal-free process (Group TF). Blood samples collected before vaccination, 21 days after the second vaccine dose, and 6 months following the first vaccine dose (Days 0, 42, and 180) were analysed using a hemagglutination inhibition (HI) assay. Safety assessments were made for the entire study period. Twenty-one days after the second dose of vaccine, both groups met the CHMP criteria for vaccine-homologous HI response (seroprotection rates/seroconversion rates ≥ 98.7%, seroconversion factor ≥ 121.9) and also for a heterologous HI response against the A/Vietnam/1194/2004 strain (seroprotection rates/seroconversion rates ≥ 81.3%, seroconversion factor ≥ 10.8). Six months after the first dose of vaccine, a marked persistence of the vaccine-homologous HI response was observed that still met one or more CHMP criteria. Pain at the injection site (Group TF 95%, Group TC 91.8%) and myalgia (Group TF 68.8%, Group TC 63.5%) were the most frequently recorded solicited symptoms. Overall, both formulations had a clinically acceptable safety profile. Administration of two doses of the AS03(A)-adjuvanted H5N1 prepandemic influenza vaccine was found to be highly immunogenic in adults with a clinically acceptable safety profile. The ability to confer cross-clade protective immunity makes it a suitable option for mitigation of the morbidity and mortality of outbreaks and pandemics due to H5N1 and drifted strains.