Immunogenicity and safety of MF59-adjuvanted H5N1 pandemic influenza vaccine in healthy infants and children: a phase 2 randomized, observer-blind, multicenter study

Zoonotic influenza pandemics can cause substantial morbidity and mortality, especially in children. The present study evaluated the immunogenicity and safety of six formulations of an MF59-adjuvanted H5N1 vaccine (aH5N1). In this phase 2, dose-ranging study, children aged 6 months to <9 years were stratified by age and randomized to one of six aH5N1 formulations containing 1.875, 3.75, or 7.5 μg HA combined with 0.25 mL MF59 (standard adjuvant content) or 0.125 mL MF59 (half adjuvant content). Vaccines were administered twice, 3 weeks apart. Immunogenicity was evaluated using hemagglutination inhibition (HI) and microneutralization (MN) assays. A total of 420 children from Europe and Asia participated in the study. Three weeks after the second vaccination, HI geometric mean ratios ranged from 13.8 to 25.0 and HI titers ≥1:40 ranged from 74.6% to 90.0% of subjects across vaccine groups. MN titers ≥1:40 were observed in all subjects, and MN titers ≥1:160 in 89.6% to 97.1% of subjects across vaccine groups. At 3 weeks and at 6 months after the second vaccination, higher titers were consistently observed in groups receiving standard MF59 content. Adverse event rates were similar across vaccine groups regardless of antigen or adjuvant content, and no safety signals were observed. Higher MF59 content was associated with a greater magnitude and persistence of immune responses but was not associated with increased reactogenicity. These data confirm that aH5N1 containing 7.5 μg HA plus 0.25 mL MF59 is immunogenic with an acceptable safety and reactogenicity profile in children.