Safety and reactogenicity of the recombinant zoster vaccine after allogeneic hematopoietic cell transplantation

Abstract

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. A nonlive adjuvanted recombinant zoster vaccine (RZV) has been developed to prevent herpes zoster (HZ), but there are no recommendations for use in this population. In this single-center prospective observational cohort study, we assessed the safety and reactogenicity of RZV, as well as incidence of graft-versus-host disease (GVHD) and confirmed cases of HZ after vaccination. Between December of 2018 and June of 2020, patients aged ≥18 years received 2 doses of RZV between 9 and 24 months after HCT, with the doses separated by ≥8 weeks. One hundred and fifty-eight patients (mean age, 55 years; 42% women) received ≥1 dose (total vaccinated cohort), and 150 patients (95%) received 2 doses (modified total vaccinated cohort). Solicited reactions occurred in 92.1% of patients (grade 3, 32.5%), owing mostly to injection site pain, which occurred in 86% (grade 3, 16%). The cumulative incidence of GVHD in the peri-vaccination period was no different than in historical controls (adjusted incidence rate ratio, 1.05; 95% confidence interval, 0.8-1.38). There were 4 cases of HZ in the total vaccinated cohort (2.5%) and 3 cases in the modified total vaccinated cohort (28.3/1000 person-years). Among recipients of allogeneic HCT, RZV was safe, tolerable, and did not increase rates of GVHD. Future clinical trials are needed to determine the immunogenicity and efficacy of RZV in this population.

Safety and Tolerability of SARS-CoV2 Emergency-Use Authorized Vaccines for Allogeneic Hematopoietic Stem Cell Transplant Recipients

“…A study published by Natori, et al reported an incidence of new or worsening GVHD in about approximately 26% of patients who received the influenza vaccine but did not have a comparator group 21 . Baumrin, et al analyzed the effect of the recombinant zoster vaccine on GVHD incidence and concluded no significant difference 22 . We also observed few cases of eosinophilia, and hepatic impairment that occurred after the vaccination, however, it is difficult to ascribe causality to the vaccines due to the retrospective nature of this study.…”

Cellular Immune Response after Vaccination with an Adjuvanted, Recombinant Zoster Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients

“…The current study is not suitable to define if vaccination in allogeneic HSCT recipients was protective, because this warrants a larger study cohort and a placebo control group. However, a previous study on allogeneic HSCT recipients determined the rate of shingles following two doses of Shingrix™ [ 28 ]. The authors described that 3 out of 150 patients suffered from shingles (28.3/1000 person-years); which appears as low as compared to 41% of VZV reactivations at a median of 227 days (range 45–346 days) post-transplantation [ 8 ].…”

Adjuvanted recombinant zoster vaccine in adult autologous stem cell transplant recipients: polyfunctional immune responses and lessons for clinical practice

“…While smaller studies showed that RZV (administered at a median 8–9 months post-transplant) was also well-tolerated in allogenic HSCT recipients, it was less immunogenic than in autologous HSCT recipients. 31 , 32 However, administration of RZV before full immune reconstitution as well as its efficacy are yet to be evaluated in allogenic HSCT recipients.…”