Safety and immunogenicity of ascending doses of influenza A(H7N9) inactivated vaccine with or without MF59®

Introduction: While it remains impossible to predict the timing of the next influenza pandemic, novel avian influenza A viruses continue to be considered a significant threat. Methods: A Phase II study was conducted in healthy adults aged 18-64 years to assess the safety and immunogenicity of two intramuscular doses of pre-pandemic 2017 influenza A(H7N9) inactivated vaccine administered 21 days apart. Participants were randomized (n = 105 in each of Arms 1-3) to receive 3.75 mu g, 7.5 mu g or 15 mu g of hemagglutinin (HA) with MF59 (R) adjuvant, or 15 mu g of HA unadjuvanted vaccine (n = 57, Arm 4). Results: The three MF59 adjuvanted vaccines and the 15 mu g unadjuvanted vaccine were safe and well-tolerated. Little antibody activity was detected against the A(H7N9) vaccine antigen after the first vaccination across study Arms. After second vaccination, the three adjuvanted Arms showed increases in hemagglutination inhibition (HAI), neutralizing (Neut), and neuraminidase inhibition (NAI) geometric mean titers (GMT), peaking at 21 days post second vaccination. The percentage of participants with titer >= 1:40 and seroconversion rates for HAI were 30-43 % and 0 for the adjuvanted Arms and the unadjuvanted Arm, respectively. Antibody responses against antigenically drifted A(H7N9) strains A/Shanghai/2/2013 and A/Guangdong/17SF003/2016 showed similar trends. Exploratory linear modeling of HAI and Neut responses post second vaccination revealed significantly lower log antibody titers among older participants (aged 35-49 and 50-64 years) compared to participants aged 18-34 years after adjusting for study vaccination, BMI, sex, and prior seasonal influenza vaccination. Post second vaccination, participants who received seasonal influenza vaccination in at least one of the two previous seasons had significantly lower log antibody titers than participants who did not. Conclusion: Adjuvanted doses of vaccine provided higher antibody responses, on average, than the 15 mu g unadjuvanted vaccine. Proportion of participants achieving seroconversion and antibody titers >= 40 remained below 50 % in all study Arm.