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^®-adjuvanted, A/H5N1 vaccine (aH5N1c; AUDENZ™) 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 μg and 3.75 μg 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 μg 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.

A cell-based process may be better suited for vaccine production during a highly pathogenic avian influenza (HPAI) pandemic. This was a phase 3, randomized, controlled, observer-blind, multicenter study evaluated safety, immunogenicity, and lot-to-lot consistency of two doses of a MF59-adjuvanted, H5N1 influenza pandemic vaccine manufactured on a cell culture platform (aH5N1c) in 3196 healthy adult subjects, stratified into two age groups: 18 to <65 and ≥65 years. Immunogenicity was measured using hemagglutination inhibition (HI) titers. HI antibody responses increased after the first aH5N1c vaccine dose, and 3 weeks after the second vaccination (Day 43), age-appropriate US Center for Biologics Evaluation and Research (CBER) and former European Medicines Authority Committee for Medicinal Products for Human Use (EMA CHMP) immunogenicity criteria were met. Six months after the first vaccination, HI titers were above baseline but no longer met CBER and CHMP criteria. No relevant changes over time were seen in placebo subjects. Solicited AEs were more frequent in the active treatment than the placebo group, primarily due to injection site pain. No serious adverse events (SAEs) related to aH5N1c- were reported. aH5N1c influenza vaccine elicited high levels of antibodies following two vaccinations administered 21 days apart and met both CBER and former CHMP immunogenicity criteria at Day 43 among both younger and older adults with a clinically acceptable safety profile. Consistency of the three consecutive aH5N1c vaccine lots was demonstrated (NCT02839330).

Influenza pandemics pose a serious risk to the global population, with the potential for high morbidity and mortality. An adjuvanted H5N1 vaccine (aH5N1) has been approved for prophylaxis against the avian influenza virus H5N1, which is a likely cause of future pandemics. In this phase-III, stratified, randomized, controlled, observer-blind, multicenter study, we evaluated the safety and immunogenicity of aH5N1 in four separate groups of adults: adults 18–60 years of age who were healthy or had high-risk medical conditions and older adults ≥61 years of age who were healthy or had high-risk medical conditions. Subjects were randomly assigned to aH5N1 or the comparator, adjuvanted trivalent seasonal influenza vaccine (aTIV). Antibody responses to aH5N1 were increased in all four subgroups and, within each age stratum, largely consistent between healthy subjects and those with medical conditions. Injection-site pain was reported by 66–73% of younger and 36–42% of older–aH5N1 recipients, and fatigue and myalgia were reported by 22–41% of subjects across age and health subgroups. No serious adverse events or deaths were considered related to the study vaccine. In conclusion, aH5N1 increased antibody responses regardless of age or health status and demonstrated a clinically acceptable safety and tolerability profile.

Background: Pandemic influenza may cause substantial morbidity and mortality, especially in older adults and those with immunosuppressive conditions. Methods: In this phase 3, stratified, randomized, controlled, observer-blind, multicenter trial, we evaluated the safety, tolerability, and immunogenicity of an adjuvanted H5N1 vaccine (aH5N1) vs. active control (MF59-adjuvanted trivalent seasonal inactivated influenza vaccine [aTIV]) in 539 adults aged 18–60 and ≥61 years. Participants were further stratified into subgroups that were healthy (18–60 years, n = 91; ≥61 years, n = 89) or had prespecified immunosuppressive conditions (18–60 years, n = 180; ≥61 years, n = 179). Antibody responses were measured with microneutralization and single radial hemolysis (SRH) assays. Results: aH5N1 increased antibody responses in healthy persons and those with immunosuppressive conditions in both age groups, with SRH geometric mean ratios (GMRs) > 2.5 and >2.0 in participants aged 18–60 and ≥61 years, respectively, meeting former Committee for Medicinal Products for Human Use (CHMP) criteria. Responses measured with the microneutralization and SRH assays were consistent with previous studies of aH5N1. Conclusions: The aH5N1 vaccine had a clinically acceptable safety and tolerability profile with an AE profile comparable to that observed in previous aH5N1 studies. These findings support the viability of aH5N1 as a pre-pandemic influenza vaccine for the immunization of at-risk individuals when an antigenically matched pandemic influenza vaccine is not yet available.

Past influenza pandemics caused by zoonotic influenza strains have resulted in considerable morbidity and mortality due to a lack of pre-existing immunity in the human population.1,2 Typically, pan...