Rapid Immunization Against H5N1: A Randomized Trial Evaluating Homologous and Cross-Reactive Immune Responses to AS03A-Adjuvanted Vaccination in Adults

Background. Accelerated immunization schedules may help gain early control of influenza pandemics. We investigated different schedules of an AS03A-adjuvanted H5N1 vaccine. Methods. This phase II, open-label, 6-month study randomized participants (aged 18-64 years) to 2 vaccine doses administered 21 (standard schedule), 14, or 7 days apart, or on the same day. Coprimary end points were that the lower limit of the 98.75% confidence interval 14 days after the last dose must be (1) > 40% for seroconversion rate (SCR) (Center for Biologics Evaluation and Research [CBER] criterion) and (2) > 50% for seroprotection rate (SPR) (attainment rate for reciprocal hemagglutination inhibition titers >= 40, protocol-defined criterion) for the vaccine homologous strain (A/Indonesia/5/2005). European Committee for Human Medicinal Products (CHMP) immunogenicity criteria were also evaluated. Results. Coprimary end points were achieved (lower 98.75% confidence intervals exceeded defined values). Titers were highest with the standard schedule. Nevertheless, CBER SCR, protocol-defined SPR, and CHMP criteria were met with all schedules for the A/Indonesia/5/2005 strain. There were no significant differences between age groups (18-40 vs 41-64 years). Immune response was robust against drift variants A/turkey/Turkey/1/2005 and A/Vietnam/1194/2004. Conclusions. The AS03(A)-adjuvanted H5N1 vaccine in accelerated schedules offers a robust immune response against vaccine homologous and drift variant strains, allowing consideration of compressed vaccination intervals. Clinical Trials Registration. NCT00695669.