Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: A phase I-II randomized trial

Objective: Highly pathogenic avian influenza A virus H5N1 has the potential to cause a pandemic. Many prototype pandemic influenza A (H5N1) vaccines had been developed and well evaluated in adults in recent years. However, data in children are limited. Herein we evaluate the safety and immunogenicity of adjuvanted split-virion and whole-virion H5N1 vaccines in children. Methods: An open-labelled phase I trial was conducted in children aged 3-11 years to receive aluminum adjuvated, split-virion H5N1 vaccine (5-30 mu g) and in children aged 12-17 years to receive aluminum-adjuvated, whole-virion H5N1 vaccine (5-15 mu g). Safety of the two formulations was assessed. Then a randomized phase II trial was conducted, in which 141 children aged 3-11 years received the split-virion vaccine (10 or 15 mu g) and 280 children aged 12-17 years received the split-virion vaccine (10-30 mu g) or the whole-virion vaccine (5 mu g). Serum samples were collected for hemagglutination-inhibition (HI) assays. Findings: 5-15 mu g adjuvated split-virion vaccines were well tolerated in children aged 3-11 years and 5-30 mu g adjuvated split-virion vaccines and 5 p.,g adjuvated whole-virion vaccine were well tolerated in children aged 12-17 years. Most local and systemic reactions were mild or moderate. Before vaccination, all participants were immunologically nave to H5N1 virus. Immune responses were induced after the first dose and significantly boosted after the second dose. In 3-11 years children, the 10 and 15 mu g split-virion vaccine induced similar responses with 55% seroconversion and seroprotection (HI titer >= 1:40) rates. In 12-17 years children, the 30 p.,g split-virion vaccine induced the highest immune response with 71% seroconversion and seroprotection rates. The 514 whole-virion vaccine induced higher response than the 10 mu g split-virion vaccine did. Interpretation: The aluminum-adjuvanted, split-virion prototype pandemic influenza A (H5N1) vaccine showed good safety and immunogenicity in children and 30 mu g dose induced immune response complying with European Union licensure criteria. [ClinicalTrials.gov identifiers: NCT00900588 and NCT00900991]. (C) 2010 Elsevier Ltd. All rights reserved.