Recombinant vs Standard Influenza Vaccine in Adults With Severe Obesity: A Randomized Clinical Trial.
BACKGROUND: Individuals with severe obesity are at increased risk of severe influenza and may have impaired immune responses to vaccination. Recombinant influenza vaccine (RIV) may provide enhanced protection compared with egg-based standard-dose influenza vaccine (SD), but data in this high-risk population are limited. METHODS: The AP-HP FLUO trial (NCT05409612) was an open-label, randomized clinical trial conducted in 15 centers in France (November 2022-March 2023) with 6 months of follow-up. Adults with BMI ≥35 kg/m2 were randomized 1:1 to receive RIV or SD, using minimization by center, age (<50 vs ≥50 years), and BMI (<40 vs ≥40 kg/m2). The primary outcome was the ratio (RIV/SD) of geometric mean hemagglutinin-inhibition (HAI) titers (GMTs) for 4 influenza strains 28 days after vaccination. Safety and reactogenicity were also assessed. RESULTS: A total of 206 participants were included (104 RIV, 102 SD). Median age was 50 years, 60.2% were women, and median BMI was 41.0 kg/m2. At Day 28, GMT ratios favored RIV for A/H1N1 (1.6; 95% CI, 1.1-2.3), A/H3N2 (2.0; 95% CI, 1.3-3.2), and B/Yamagata (1.3; 95% CI, 1.0-1.8), but not for B/Victoria (0.9; 95% CI, 0.6-1.3). The effect did not vary significantly across the different age and BMI groups. By Day 180, titers did not differ significantly. Reactogenicity and safety profiles were similar between groups. CONCLUSIONS: In adults with severe obesity, RIV elicited stronger short-term humoral immune responses than an egg-based standard-dose vaccine, suggesting potential additional benefit for influenza prevention in this vulnerable population.