Real-World Effectiveness of Recombinant Zoster Vaccine in Allogeneic Hematopoietic Cell Transplant Recipients

Herpes zoster (HZ) is a frequent and clinically significant complication following allogeneic hematopoietic cell transplantation (allo-HCT), arising from delayed immune reconstitution and impaired varicella-zoster virus-specific immunity. Although acyclovir prophylaxis reduces early risk, prolonged use is often limited by toxicity and poor adherence. The recombinant zoster vaccine (RZV), a non-live adjuvanted subunit vaccine, has demonstrated high efficacy in immunocompetent adults and in several immunocompromised populations; however, real-world data in allo-HCT recipients remain scarce. To evaluate the real-world effectiveness of RZV in preventing HZ among allo-HCT recipients and to assess vaccine performance across clinical subgroups and in relation to antiviral prophylaxis. We conducted a retrospective cohort study of 506 allo-HCT recipients at a tertiary transplantation center, including 152 patients who completed the two-dose RZV series and 354 historical unvaccinated controls. The primary outcome was HZ incidence within 2 years after transplantation. Time-dependent Cox regression models were applied to estimate adjusted hazard ratios (aHRs), with RZV and acyclovir modelled as time-varying covariates. Competing risk and 9-month landmark analyses were performed to validate robustness. The 2-year cumulative HZ incidence was 19.7% in unvaccinated versus 5.9% in vaccinated patients (Gray's P < .001). RZV significantly reduced HZ risk (aHR 0.287, 95% confidence interval [CI] 0.131 to 0.627), corresponding to 71.3% effectiveness, consistent across subgroup analyses. Continued acyclovir prophylaxis was independently protective (aHR 0.323, 95% CI, 0.147 to 0.711). Importantly, no HZ events occurred in RZV recipients who discontinued acyclovir prematurely. Thirteen of 76 HZ cases (17.1%) met the criteria for complicated disease, strongly associated with chronic graft-versus-host disease and HLA mismatch; however, no significant effect of RZV was observed. RZV demonstrated substantial effectiveness in reducing HZ risk among allo-HCT recipients in real-world clinical practice. These findings provide compelling evidence for incorporating RZV into after transplantation preventive care as a valuable complement to, or alternative to, traditional antiviral prophylaxis strategies.