Immunogenicity and safety of MF59-adjuvanted seasonal influenza vaccine and pandemic influenza A (H1N1) vaccine in children : a systematic review

Abstract

Context：Children have very high morbidity and hospitalization rates from seasonal and pandemic influenza. They also play a major role in the spread of influenza disease. It has been reported conventional (non-adjuvanted) inactivated influenza vaccines have low efficacy, while MF59-adjuvanted vaccines could be more efficient than conventional vaccines. But the immunogenicity and safety of MF59-adjuvanted vaccines in children have not been well established. So the objectives of this study are to examine immunogenicity and safety of MF59-adjuvanted seasonal influenza and pandemic influenza A (H1N1) vaccines in children and assess whether MF59-adjuvanted influenza vaccine is better than non-adjuvanted vaccine.

Methods: A comprehensive search of PubMed, MEDLINE and Cochrane Library was performed without time and language restrictions. Randomized clinical trials, which assess immunogenicity and/or safety of MF59 adjuvanted seasonal influenza vaccine and pandemic influenza A (H1N1) vaccine in children, were identified. The quality of these selected studies was evaluated using Jadad Score and Cochrane Handbook of Systematic Reviews of Interventions. The criteria of seroprotection rate (SPR), seroconversion rate (SCR) and Geometric mean titer ratio (GMTR) implemented by the European Committee for Medicinal Products for Human Use (CHMP) was used as the standard criteria to evaluate immunogenicity of vaccines.

Results: 12 studies were identified in total, 5 on MF59-adjuvanted trivalent seasonal influenza vaccines, 1 on MF59-adjuvanted monovalent H3N2 influenza vaccines and 6 on MF59-adjuvanted pandemic H1N1 influenza vaccines. Immunogenicity: For MF59-adjuvanted influenza vaccines, immunogenecity of homologous strains in terms of influenza H1N1, H3N2 can meet all three criteria of CHMP after the first dose in all age cohorts (SPR [77, 100], SCR [43, 100] and GMTR [7, 41]), whereas a second dose was needed for B antigen. For non-adjuvanted influenza vaccines, a second dose was needed for all three strains to meet all the criteria (GMTR [3.95, 97], SPR [70, 100] and SCR [42, 99]), with the exceptions of three trials related to B strain. When it comes to heterologous strains, a second dose was needed for both MF59-adjuvanted trivalent seasonal influenza and non-adjuvanted trivalent seasonal vaccines. However, MF59-adjuvanted vaccine can induce greater immune responses especially for B strain after the second dose (SPR [71, 100], GMTR [3.35, 16] and SCR [55, 96]), while the immunogenicity for non-adjuvanted vaccine was still poor with 7 out of 11 trials cannot meet all three criteria of CHMP.

Safety: MF59-adjuvanted influenza vaccines often induced mild and transient reactions. Conclusions: MF59-adjuvanted seasonal influenza vaccine and pandemic influenza A (H1N1) vaccine have good immunogenicity and safety profile, and MF59-adjuvanted influenza vaccine is better than non-adjuvanted influenza vaccine in terms of immunogenicity, whether it is trivalent vaccine or monovalent vaccine.