Zoster Vaccine to Enhance Protection Against Zoster in Solid-organ Transplantation

Herpes zoster (named zoster thereafter) results from reactivation of latent varicella-zoster virus (VZV) and represents a major cause of morbidity in immunocompromised populations. Among SOT recipients, the incidence of zoster is estimated to be 3-10 times higher than in the general population. In these patients, zoster is often more severe and associated with disseminated disease, and a higher risk of post-herpetic neuralgia. These complications may not only impair quality of life but also increase healthcare utilization and risk of graft dysfunction.

The recombinant zoster vaccine (RZV, Shingrix®) has shown high efficacy in immunocompetent adults. In immunocompromised populations, RZV demonstrated safety and moderate immunogenicity, including in patients who received autologous stem cell transplantation and renal transplantation. However, breakthrough infections remain frequent, affecting approximately 30% of immunocompromised patients despite prior vaccination.

The immunological mechanisms underlying these breakthrough cases likely include waning immunity and the effects of chronic immunosuppressive therapy. Since transplant recipients must receive long-term immunosuppressive drugs to prevent graft rejection, their immune system is less capable of maintaining effective vaccine-induced immunity. We hypothesize that administering an additional booster dose of RZV after transplantation could restore or enhance immune responses, leading to improved protection against zoster.

To date, no systematic clinical trial has evaluated this booster approach in solid-organ transplantation. The ZEST pilot trial therefore addresses an important evidence gap, with the potential to establish a novel vaccination strategy for this high-risk population. The trial will generate key immunological data to inform the feasibility, safety, and biological plausibility of post-transplant booster vaccination, laying the groundwork for a future multicentre randomized trial with clinical endpoints such as incidence of zoster.

SOT recipients will be identified through the transplantation center and approached during routine follow-up visits, or via mailed invitations. After receiving study information and providing written or electronic consent, participants will be randomized in a 2:1 ratio to receive a booster dose of RZV or no intervention. Randomisation and vaccination will take place either during a routine outpatient visit or in a dedicated vaccination unit to minimize additional workload for clinical staff. Blood samples will be collected at four predefined time points: at the time of vaccination (baseline) and at 1, 6, and 12 months after the booster dose. An additional blood sample at the time of transplantation may be obtained via the STCS biobank if available.

Participants randomized to the intervention arm will receive a single intramuscular injection of Shingrix® (0.5 mL recombinant glycoprotein E antigen with AS01B adjuvant) administered into the deltoid muscle. The booster will be administered at least 6 months after transplantation. Vaccine supply, storage (2-8°C), and accountability will be managed by the hospital pharmacy according to GCP standards.

The control group will not receive any intervention

Inclusion criteria

• Aged ≥18 years
• SOT recipient who has received two doses of the Shingrix® vaccine (primary vaccination).
• At least 6 months after transplantation
• At least 6 months after the completion of the Shingrix® primary vaccination series.
• At least 8 weeks have elapsed since any treated episode of acute allograft rejection or At least 6 months if B-cell depleting antibodies (e.g. rituximab, alemtuzumab) was used as part of the treatment.
• Signature of the written informed consent.

Exclusion criteria

• Acute febrile illness or active infection at the time of enrolment, as determined by the investigator (patients can be enrolled in a later stage).
• Known hypersensitivity to any component of RZV.
• Willing to become pregnant