Immunogenicity and safety of higher-dose cell-based adjuvanted quadrivalent influenza vaccines: Combined results of randomised, controlled dose-finding and dose-confirmation studies

The optimal formulation of an adjuvanted cell-based quadrivalent influenza vaccine (aQIVc) was investigated in Phase 2, observer-blind, multicentre, dose-finding (V201_01, NCT04782323) and dose-confirmation (V201_07, NCT05501561) studies in participants aged ≥50 years. In V201_01, participants were randomised to one of seven investigational aQIVc formulations or non-adjuvanted QIVc (15 μg haemagglutinin antigen [HA] per strain). Investigational formulations contained 15, 30, or 45 μg HA per strain, and 1×, 2×, and 3× the dose of MF59 adjuvant included in Fluad®. In V201_07, participants were randomised to aQIVc [45,1×], aQIVc [45,2×], QIVc [45,0×: 45 μg HA, 0×MF59] or QIVc [15,0×: 15 μg HA, 0× MF59]. Primary objective: to assess the immunogenicity of aQIVc formulations vs. QIVc 28 days post-vaccination. In V201_01, 838 participants (47.3% aged ≥65 years; 56.6% female; 55.9% White) were exposed. Generally, covariate-adjusted geometric mean titre ratios (GMTr) of aQIVc vs. QIVc at Day 29 (per-protocol set [PPS; n = 810]) increased with antigen and adjuvant dose but were similar between 2× and 3× adjuvant. In V201_07, 1051 participants (47.9% aged ≥65 years; 58.0% female; 83.7% White) were exposed (PPS; n = 1022). GMTr for aQIVc [45,2×] vs. QIVc [15,0×] ranged from 1.27 (95% confidence interval [CI], 1.04, 1.55) to 1.86 (1.52, 2.27) and were superior (lower limit of 95% CI >1.0) for all strains. GMTr of aQIVc [45,2×] vs. QIVc [45,0×] were superior for A/H1N1, A/H3N2, and B/Yamagata, and non-inferior for B/Victoria. Neither study presented safety concerns. In V201_07, rates of solicited adverse events (Day 1-7 post-vaccination) were highest with aQIVc [45,2×] (71.1%) and lowest with QIVc [15,0×] (50.4%); most events were mild (Grade 1) or moderate (Grade 2) severity across all groups. aQIVc [45,2×] demonstrated the highest immune response of all formulations tested, with no safety concerns, and was selected for further investigation in a Phase 3 study (NCT06015282). Clinical trial registry: NCT04782323 (https://clinicaltrials.gov/study/NCT04782323; registered date 2021-03-01), NCT05501561 (https://clinicaltrials.gov/study/NCT05501561; registered date 2022-08-11).