Randomized, Multicenter Trial of a Single Dose of AS03-adjuvanted or Unadjuvanted H1N1 2009 Pandemic Influenza Vaccine in Children 6 Months to <9 Years of Age

Background: During the 2009-2010 influenza pandemic, we evaluated the immunogenicity and safety of different H1N1 2009 pandemic influenza vaccines delivering various viral hemagglutinin (HA) doses with or without AS03 (a tocopherol oil-in-water emulsion-based adjuvant system) in children (NCT00976820). Methods: Three hundred twenty-two healthy children 6 months to <9 years of age were randomized to receive 2 doses of nonadjuvanted (15 mu g or 7.5 mu g HA) or adjuvanted vaccine (3.75 mu g HA/AS03(A) or 1.9 mu g HA/AS03(B)), 21 days apart. Blood samples before and after each dose were tested for immune responses using hemagglutination inhibition and microneutralization assays. Safety assessments were done up to day 385. Results: The first dose of both AS03-adjuvanted vaccines elicited strong immune responses (seroprotection rates: 98.3%/99.0%; seroconversion rates: 94.9%/97.0%; geometric mean fold rises: 36.2/33.6), which were higher post-dose 2 (seroprotection rate: 100.0%/100%; seroconversion rate: 100.0%/98.8%; geometric mean fold rise: 157.1/151.6), meeting European regulatory criteria on days 21 and 42. The nonadjuvanted 15 mu g HA vaccine also met the regulatory criteria after each dose; the 7.5 mu g HA vaccine met them only post-dose 2. Six months post-dose 1, all vaccines except the nonadjuvanted 7.5 mu g HA vaccine met European regulatory criteria. Neutralizing antibody response paralleled the hemagglutination inhibition immune response after each dose. Pain at the injection site, lasting 2-3 days, was more common following adjuvanted than nonadjuvanted vaccination. Conclusions: AS03-adjuvanted H1N1 2009 pandemic influenza vaccine (3.75 mu g or 1.9 mu g HA), administered as 2 doses, was highly immunogenic, induced long-term immune response to 6 months, with a clinically acceptable safety profile in children aged 6 months to < 9 years of age.