A Randomized, Double-Blind Clinical Trial of One vs Two Doses of High-Dose Influenza Vaccine in Solid Organ...

Solid organ transplant recipients (SOTRs) exhibit suboptimal immune responses to standard-dose influenza vaccines. High-dose (HD) vaccines and booster strategies show promise, but the optimal vaccination approach for SOTRs remains undefined. We sought to evaluate a double vs a single HD influenza vaccine regimen, with the hypothesis that the double HD would yield superior immunogenicity.

This randomized clinical trial during the 2023-2024 and 2024-2025 influenza seasons compared the immunogenicity, clinical outcomes, and safety of 2 HD 1 month apart vs 1 HD influenza vaccines in 65 adult SOTRs at the University of Minnesota. The study comprised 3 visits: baseline, 1-month follow-up, and 4-month follow-up.

The primary analysis showed greater but no statistically significant geometric mean fold rises (GMFRs) of ID₈₀ neutralizing and binding antibody titers from baseline to 4-month follow-up in the 2 HD group compared with the 1 HD group. However, exploratory analyses focusing on the period before to after the second injection (1-4 months) showed statistically significant differences in GMFRs for both ID₈₀ neutralizing and binding titers of most strains when comparing the 2 groups. Two participants from the 1 HD group developed laboratory-confirmed influenza. Adverse event frequency was balanced between groups, with reactogenicity symptoms within 7 days of injection being grade 1.

While a single HD vaccine provides an initial immune response, an HD booster appeared to improve overall immune responses to influenza strains contained in the vaccine formulation, although confirmation in larger, adequately powered studies is needed. Clinical Trials Registration. NCT05663463.