Immunogenicity and safety of adjuvanted recombinant zoster vaccine in chronically immunosuppresed adults following renal transplant: A phase III, randomized clinical trial

Abstract

Background: The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. Methods: In this phase III, randomized (1:1), observer-blind, multicenter trial (NCT02058589), RT recipients were enrolled and received 2 doses of RZV or Placebo 1-2 months (M) apart 4-18M post-transplant. Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post-dose 1, and 1M and 12M post-dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post-each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post-dose 2. Results: 264 participants (RZV: 132; Placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across post-vaccination time points and persisted above pre-vaccination baseline 12M post-dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, SAEs, and pIMDs were similar between groups. Conclusions: RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M post-vaccination. No safety concerns arose.