Strain-specific influenza vaccine immunogenicity in adults with severe asthma receiving biologic therapy: a real-world baseline-adjusted HAI study

Background Evidence on influenza vaccine immunogenicity during biologic treatment for severe asthma remains limited, particularly in adults treated in routine clinical practice. Methods In this prospective single-centre observational study, we analysed pre- and post-vaccination haemagglutination-inhibition (HAI) titres in 147 adults with asthma who received Grippol Quadrivalent during the 2023–2024 season: 126 patients with severe asthma receiving ongoing biologic therapy and 21 asthma controls not receiving biologic therapy. Blood was obtained before vaccination and 4–6 weeks after vaccination. For each vaccine strain, log2(post-vaccination HAI) was modelled using analysis of covariance with study group and the corresponding log2(pre-vaccination HAI) titre as predictors. The group coefficient was back-transformed to an adjusted geometric mean ratio (GMR; biologic therapy/control). Results Adjusted GMRs were 0.61 (95% CI 0.33–1.13; P = 0.113) for A/H1N1/Victoria, 1.08 (0.64–1.81; P = 0.779) for A/H3N2/Darwin, 0.46 (0.23–0.94; P = 0.032) for B/Austria, and 0.59 (0.34–1.05; P = 0.073) for B/Phuket. Conclusion Baseline-adjusted estimates differed numerically across strains, but between-strain heterogeneity was not formally tested.B/Austria yielded a nominally lower adjusted titre (P = 0.032; Holm-adjusted P = 0.128), but not after additional adjustment for age and sex (GMR 0.54, 95% CI 0.28–1.05; P = 0.068); confidence intervals for the other three strains included unity; all findings are exploratory. These observational data extend randomized evidence from individual biologics to an adult real-world severe-asthma cohort.