Immunogenicity and safety of an MF59-adjuvanted cell-derived higher-dose quadrivalent influenza vaccine (aQIVc) in adults aged 50 years or older: a phase 3 randomised controlled trial

Summary:

"Findings: Between Nov 3, 2023, and Jan 30, 2024, 7699 adults aged 50 years or older were randomly assigned, of whom 7677 were included in the all exposed set (aQIVc, n=3283; aQIV, n=2205; QIVr, n=2189; as randomised) and 7419 were in the per-protocol set (aQIVc, n=3175; aQIV, n=2129; QIVr, n=2115). Lot-to-lot consistency criteria were fully met. aQIVc was non-inferior and superior (lower bound 97·5% CI of day-29 GMT ratio was more than 1·0; secondary objective) to aQIV at day 29: GMT ratio was 1·53 (97·5% CI 1·43 to 1·64) for A/H1N1, 1·22 (1·15 to 1·30) for A/H3N2, 1·73 (1·63 to 1·85) for B/Victoria, and 1·71 (1·63 to 1·80) for B/Yamagata, and corresponding seroconversion rate differences were 16·8% (97·5% CI 13·9 to 19·8), 9·5% (6·4 to 12·5), 21·9% (18·8 to 24·9), and 24·3% (21·3 to 27·2), respectively. Compared with QIVr, non-inferiority criteria were met for three strains, but not A/H3N2: GMT ratio was 0·93 (97·5% CI 0·87 to 1·00) for A/H1N1, 0·69 (0·65 to 0·74) for A/H3N2, 1·41 (1·33 to 1·50) for B/Victoria, and 1·33 (1·27 to 1·40) for B/Yamagata, and seroconversion rate differences were 1·5% (97·5% CI –1·2 to 4·3), –7·4% (–10·3 to –4·6), 11·6% (8·5 to 14·7), and 13·4% (10·3 to 16·5), respectively. aQIVc was well tolerated; despite higher rates of local and systemic adverse events versus aQIV and QIVr, most were mild-to-moderate, transient, and self-resolved. Serious adverse events were low across all vaccine groups (days 1–181; 91 [2·8%] of 3282 with aQIVc; 78 [3·5%] of 2204 with aQIV; and 64 [2·9%] of 2191 with QIVr)."

"Interpretation: In adults aged 50 years or older, aQIVc was non-inferior and superior to aQIV for all four influenza strains and non-inferiority criteria for aQIVc versus QIVr were met for A/H1N1 and both B strains, but not A/H3N2. No safety concerns were identified."