A Randomized, Double-Blind Clinical Trial of One vs. Two Doses of High-Dose Influenza Vaccine in Solid Organ Transplant Recipients
Kevin Escandón, Sophia Q Tang, Jamie Forschmiedt, Kwang Low, Bob C Lin, Jenny Lu Wang, Mike Castro, Sandeep Narpala, Leonid A Serebryannyy, Jodi Anderson, Jarrett Reichel, Richard A Koup, Kyle D Rudser, Hareesh Singam, Joshua Rhein, Susan Kline, Timothy W Schacker, Lauren M FontanaAbstract
Background
Solid organ transplant recipients (SOTRs) exhibit suboptimal immune responses to standard-dose (SD) 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.
Methods
This randomized clinical trial during the 2023–2024 and 2024–2025 influenza seasons compared the immunogenicity, clinical outcomes, and safety of 2 HD one month apart vs. 1 HD influenza vaccines in 65 adult SOTRs at the University of Minnesota. The study comprised three visits: baseline, 1-month follow-up, and 4-month follow-up.
Results
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 month to 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.
Conclusions
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.