Randomized Trial of a MF-59 Adjuvanted Influenza Vaccine in Kidney Transplant Recipients.

Abstract

Introduction: Influenza vaccine has suboptimal immunogenicity in transplant patients. Influenza vaccine containing an oil-in-water emulsion adjuvant (MF-59) can theoretically attract greater numbers of inflammatory cells to the site of injection leading to enhanced immunogenicity. However, alloimmunization may be a concern with adjuvanted vaccines. We conducted a randomized trial of adjuvanted vs. nonadjuvanted influenza vaccine. Methods: Adult kidney transplant patients were randomized 1:1 to receive an intramuscular injection of 2012-13 influenza vaccine with or without MF59 adjuvant. Sera were collected pre- and 4 weeks post-immunization for hemagglutination inhibition assay to the 3 antigens contained in the vaccine. The presence of HLA alloantibody was also determined by Luminex single-antigen bead assay in patients who received adjuvanted vaccine. Results: We randomized 68 patients and 60 (29 nonadjuvanted; 31 adjuvanted) had complete samples available at followup. Demographics including age, gender, time from transplant, and immunosuppression were similar in both groups. Median age was 49.7 years and time from transplant to immunization was 8.1 years (range 0.73-33). Seroconversion to at least one of 3 influenza antigens was present in 71.0% vs. 55.2% in adjuvanted vs. nonadjuvanted vaccine respectively (p=0.21). Serconversion to influenza A/H1N1, A/H3N2 and B was 45.2%, 48.4%, 32.3% in adjuvanted vaccine and 48.3%, 34.5%, 24.1% respectively for nonadjuvanted vaccine (p=NS). There were also no significant differences in geometric mean titers and seroprotection rates between the groups. In univariate analysis, patients on MMF had lower likelihood of seroconversion (55.6% vs. 86.7% seroconversion on MMF vs. no MMF; p=0.03). Seroconversion rates were especially low in those on MMF ≥2g daily (44.4% vs. 71.4%; p=0.047). Safety analysis in 61/68 available patients showed that local tenderness occurred more commonly after adjuvanted vaccine (p=0.037). Donor specific HLA antibody and nonspecific antibodies were present post-vaccination in 7/30 (23.3%) and 10/30 (33.3%) respectively. However, these antibodies were all present in pre vaccination sera. Conclusions: Adjuvanted vaccine did not offer significant benefits over standard influenza vaccine with regards to immunogenicity. The adjuvanted vaccine appeared to be safe and no new alloantibody development was observed. DISCLOSURES:Kumar, D.: Grant/Research Support, Roche. Humar, A.: Grant/Research Support, Roche.