A Double-Blind, Randomized Trial of High-Dose vs Standard-Dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients

Background: The annual standard-dose (SD) influenza vaccine has suboptimal immunogenicity in solid organ transplant recipients (SOTRs). Influenza vaccine that contains higher doses of antigens may lead to greater immunogenicity in this population. Methods: We conducted a randomized, double-blind trial to compare the safety and immunogenicity of the 2016-2017 high-dose (HD; FluzoneHD, Sanofi) vs SD (Fluviral, GSK) influenza vaccine in adult SOTRs. Preimmunization and 4-week postimmunization sera underwent strain-specific hemagglutination inhibition assay. Results: We enrolled 172 patients who received study vaccine, and 161 (84 HD; 77 SD) were eligible for analysis. Seroconversion to at least 1 of 3 vaccine antigens was present in 78.6% vs 55.8% in HD vs SD vaccine groups (P < .001), respectively. Seroconversions to A/ H1N1, A/H3N2, and B strains were 40.5% vs 20.5%, 57.1% vs 32.5%, and 58.3% vs 41.6% in HD vs SD vaccine groups (P = .006, P = .002, P = .028, respectively). Post-immunization geometric mean titers of A/H1N1, A/H3N2, and B strains were significantly higher in the HD group (P = .007, P = .002, P = .033). Independent factors associated with seroconversion to at least 1 vaccine strain were the use of HD vaccine (odds ratio OR, 3.23; 95% confidence interval CI, 1.56-6.67) and use of mycophenolate doses <2 g daily (OR, 2.76; 95% CI, 1.12-6.76). Conclusions: HD vaccine demonstrated significantly better immunogenicity than SD vaccine in adult transplant recipients and may be the preferred influenza vaccine for this population. Clinical Trials Registration: NCT03139565.