Analyses of Safety Profile and Homologous Antibody Responses to a Mammalian Cell-Based, MF59-Adjuvanted, A/H5N1, Pandemic Influenza Vaccine across Four Phase II/III Clinical Trials in Healthy Children, Adults, and Older Adults

Modern cell culture-based technology eliminates vaccine manufactures reliance on embryonated chicken eggs, which may become compromised during an avian influenza pandemic. Four studies (total N = 6230) assessed the immunogenicity and safety of mammalian cell-based, MF59(R)-adjuvanted, A/H5N1 vaccine (aH5N1c; AUDENZ (TM)) as two doses administered on Days 1 and 22 in children (NCT01776554), adults (NCT01776541; NCT02839330), and older adults (NCT01766921; NCT02839330). Immunogenicity of formulations at 7.5 mu g and 3.75 mu g antigen per dose were assessed by hemagglutination inhibition and microneutralization assays on Days 1, 22, 43, and 183 or 387. Solicited local and systemic adverse events (AEs) were recorded for 7 days after each vaccination. Unsolicited AEs were collected for 21 days after each vaccination, and serious and other selected AEs were recorded for one year. Antibody responses after two 7.5 mu g doses met CBER licensure criteria in all age groups. Overall, an age-related response was evident, with the highest responses observed in children <3 years old. In children, antibody titers met seroconversion criteria 12 months after vaccination. MF59 allowed for antigen dose sparing. Solicited AEs were mild to moderate in nature, of short duration, and less frequent after the second dose than the first, demonstrating a favorable risk-benefit profile.