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

Abstract

Background. The annual Influenza vaccine is recommended for solid‐organ transplant recipients (SOTR) although studies have shown suboptimal immunogenic‐ity. Influenza vaccine containing higher dose antigen may lead to greater immuno‐genicity in this population. Method. We conducted a randomized, observer‐blind trial comparing the safety and immunogenicity of high dose (HD; FluzoneHD, Sanof) 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 postimmuni‐zation sera underwent strain‐specifc 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 immunogenic‐ity than SD vaccine in adult transplant recipients and may be the preferred Influenza vaccine for this population.