Safety and immunogenicity of a prototype adjuvanted inactivated split-virus influenza A (H5N1) vaccine in infants and children

ObjectiveHighly pathogenic avian influenza A virus (H5N1) is a leading candidate for the next influenza pandemic, and infants and children may play an important role in transmission in a pandemic. Our objective was to evaluate the safety and immunogenicity of a prototype inactivated, aluminium adjuvanted, split-virus, clade 1 H5N1 vaccine (A/Vietnam/1194/2004/NIBRG-14) in infants and children aged ≥6 months to <9 years.MethodsHealthy infants and children (N = 150) received two doses of 30 μg or 45 μg H5 HA with AlPO4 adjuvant 21 days apart. Serum samples were collected for virus microneutralisation (MN) and haemagglutination inhibition (HI) assays on Days 0, 21, and 42. Six-month antibody persistence following second vaccine dose was assessed by MN, and cross-reactive HI antibodies to a clade 2 variant strain (INDO5/RG2) were evaluated at Day 42.FindingsBoth formulations were well-tolerated. Two doses of 30 μg or 45 μg H5 HA formulations elicited strong immune responses by both MN (98–99% ≥1:20) and HI assays (95–100% ≥1:32), with 80–87% of children having MN antibody persistence (≥1:20) up to 6 months post-vaccination. Additionally, robust cross-clade HI antibody responses were elicited following two doses.InterpretationTwo doses of prototype 30 μg or 45 μg aluminium-adjuvanted, H5N1 vaccines were highly immunogenic and well-tolerated, with considerable antibody persistence 6 months after the primary vaccination course. Additional cross-clade HI antibody responses and an acceptable safety and tolerability profile support the use of the either candidate vaccine formulations in infants and children in the event of a pandemic [ClinicalTrials.gov identifiers: NCT00370864].