A Randomized Trial of High-dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients

BACKGROUND: The annual influenza vaccine is recommended for solid-organ transplant recipients (SOTR) although studies have shown suboptimal immunogenicity. Influenza vaccine containing higher dose antigen may lead to greater immunogenicity in this population. METHOD: We conducted a randomized, observer-blind trial comparing the safety and immunogenicity of high dose (HD; FluzoneHD, Sanofi) vs. standard dose (SD; Fluviral, GSK) influenza vaccine in adult SOTR. Patients were randomized 1:1 to receive the 2016–2017 influenza vaccine. Preimmunization and 4-week postimmunization sera underwent strain-specific hemagglutination inhibition assay for the three vaccine strains and an additional B strain not included in the vaccine. RESULT: We randomized 172 patients and 161 (84 HD; 77 SD) were eligible for analysis. Median age was 57 years (range 18–86) and time from transplant was 38 (range 3–1402) months. Types of transplant were kidney 67 (39.0%), liver 38 (22.1%), lung 25 (14.5%), heart 23 (13.3%), and combined 19 (11.0%). Seroconversion to at least one of the three vaccine antigens (primary outcome) was present in 78.6% vs. 55.8% in HD vs. SD vaccine, respectively (P < 0.001). Seroconversion 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 (P = 0.006, 0.002, 0.028, respectively). Postimmunization geometric mean titers of A/H1N1, A/H3N2, and B strains were significantly higher in the HD group (P = 0.007, 0.002, 0.033). Independent factors associated with seroconversion to at least one vaccine strain were the use of HD vaccine and being on mycophenolate doses less than 2 g daily (P = 0.003, 0.013, respectively). Seroconversion rate to the B strain not included in the trivalent study vaccine was also higher in the HD vaccine group (33.3% vs. 14.1%, P = 0.004). Local and systemic adverse events were similar for the two vaccines. Biopsy-proven rejection was seen in 3.4% vs. 1.2% in HD vs. SD groups, respectively (P = 0.62). Two patients in the SD vaccine group and one in the HD group developed influenza infection during the follow-up. CONCLUSION: High-dose vaccine demonstrated significantly better immunogenicity than SD vaccine in adult transplant recipients and may be the preferred influenza vaccine for this population. DISCLOSURES: D. Kumar, Sanofi: Speaker’s Bureau, Speaker honorarium. Pfizer: Speaker’s Bureau, Speaker honorarium. GSK: Grant Investigator, Grant recipient.