Immunogenicity and safety of high-dose versus double-dose quadrivalent inactivated influenza vaccine in adult kidney transplant recipients: a randomized controlled trial (2023).

Background: Solid organ transplant (SOT) recipients are at increased risk of influenza-related complications and often exhibit suboptimal vaccine responses. While both high-dose (HD) and double-dose (DD) quadrivalent inactivated influenza vaccines (QIIV) aim to enhance immunogenicity compared to the standard dose, access to HD QIIV may be limited in resource-constrained settings. We evaluated whether DD QIIV could serve as a practical alternative. Methods: We conducted open-label randomized controlled trial comparing the 2023 Southern Hemisphere HD QIIV containing 60 μg of antigen per strain with a double dose of standard QIIV containing 30 μg per strain in adult kidney transplant (KT) recipients. Pre- and 4-week post-vaccination sera were tested using strain-specific hemagglutination inhibition assays. Safety was also assessed. Findings: Eighty-eight KT recipients were randomized and 84 were eligible for analysis (42 per group); 59.5% were male, with a mean age of 46 ± 11 years, and 60.7% received deceased donor kidneys. Seroconversion (SC) to ≥1 strain was significantly higher in the HD group (95.2%) than in the DD group (69%) (P = 0.002). The absolute difference in response rate was 0.26 (95% CI, 0.12-0.40). SC rates were numerically higher in the HD group for all strains. Injection site pain and myalgia were less common in the HD group, with P = 0.040 and P = 0.043, respectively. Interpretation: HD QIIV demonstrated more favorable immunogenicity and tolerability than DD QIIV. These findings suggest that HD QIIV may be a preferable option for this population when available. Funding: This study was supported by the Research grant from Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.