Abstract
BACKGROUND: As the influenza A H1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years. METHODS: Children received 2 doses of approximately 15 or 30 µg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition titers were measured on days 0 (prevaccination), 8, 21, 29 and 42. RESULTS: A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 µg dosage elicited a seroprotective hemagglutination inhibition (≥ 1:40) in 20%, 47% and 93% of children in the 6-35 month, 3-9 year and 10-17 year age strata 21 days after dose 1 and in 78%, 82% and 98% of children 21 days after dose 2, respectively. The 30 µg vaccine dosage induced similar responses. CONCLUSIONS: The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 µg dose induced seroprotective antibody responses in most children 10-17 years of age, younger children required 2 doses, even when receiving dosages 4- to 6-fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics.