Dose-range Study of MF59-adjuvanted Versus Nonadjuvanted Monovalent A/H1N1 Pandemic Influenza Vaccine in Six- to Less Than Thirty-Six-month-old Children

Background: The successful vaccination of children 6 to 36 months of age against 2009 A/H1N1 influenza was essential to help reduce the burden of pandemic disease in both the pediatric and adult populations. Objectives: We compared the immunogenicity and safety of 4 alternative monovalent vaccine formulations to identify which provided optimal levels of seroprotection according to the US and European Union (EU) licensure criteria. Subjects and Methods: A total of 654 healthy subjects (6 to <36 months old) were given 2 vaccine doses 3 weeks apart. Participants were assigned to 1 of the 4 immunization groups, receiving MF59-adjuvanted (Novartis Vaccines, Marburg, Germany) vaccine either containing 3.75 mu g or 7.5 mu g of A/H1N1 California/7/2009 antigen, or nonadjuvanted vaccine containing 7.5 mu g or 15 mu g of antigen. Antibody titers were assessed by hemagglutination inhibition assay 3 weeks, 3 months and 1 year after immunization. Vaccine safety was monitored throughout the study. Results: After 1 dose, both adjuvanted formulations met the US and EU criteria for seroconversion; the 15 mu g nonadjuvanted vaccine met the EU criterion for seroconversion alone. The US and EU criteria for seroprotection were only met by adjuvanted groups. MF59-adjuvanted formulations alone resulted in clinically significant persisting antibody titers after 12 months. All vaccines were well tolerated. Conclusions: A single dose of MF59-adjuvanted vaccine containing 3.75 mu g A/H1N1 antigen was highly immunogenic, met both the US and EU licensure criteria and was well tolerated. These data support the suitability of this monovalent vaccine formulation for pandemic use in children 6 to <36 months of age.