Safety and Immunogenicity of MF59-Adjuvanted Cell Culture-Derived A/H5N1 Subunit Influenza Virus Vaccine: Dose-Finding Clinical Trials in Adults and the Elderly.

Background. A/H5N1 influenza viruses have high pandemic potential; consequently, vaccines need to be produced rapidly. MF59 (R) adjuvant reduces the antigen required per dose, allowing for dose sparing and more rapid vaccine availability. Methods. Two multicenter, phase II trials were conducted to evaluate the safety and immunogenicity of an MF59-adjuvanted, cell culture-derived, A/H5N1 vaccine (aH5N1c) among 979 adult (18-64 years old) and 1393 elderly (>= 65 years old) subjects. Participants were equally randomized to receive 2 full-dose (7.5 mu g of hemagglutinin antigen per dose) or 2 half-dose aH5N1c vaccinations 3 weeks apart. Outcomes were based on Center for Biologics Evaluation Research and Review (CBER) and Committee for Medicinal Products for Human Use (CHMP) licensure criteria (titers >= 1:40 and seroconversions on day 43). Solicited reactions and adverse events were assessed (www.clinicaltrials.gov: NCT01776541 and NCT01766921). Results. CBER and CHMP criteria were met by both age groups. CBER criteria for hemagglutination titers were met for the full-dose formulation. Solicited reaction frequencies tended to be higher in the full-dose group and were of mild to moderate intensity. No vaccine-related serious adverse events occurred. Conclusions. In adult and elderly participants, the full-dose aH5N1c vaccine formulation was well tolerated and met US and European licensure criteria for pandemic vaccines.