Zoster Vaccine to Enhance Protection Against Zoster in Solid-organ Transplantation (ZEST)

A Single-centre Open-label Parallel Two-arms Pilot Randomized Clinical Trial of a Booster Recombinant Zoster Vaccine in Solid-Organ Transplant Recipients

Shingles is caused by the same virus that causes chickenpox. After someone has chickenpox, the virus stays in the body and can become active again later in life. This is called shingles.

People who have received a solid organ transplant (such as a kidney, liver, or heart transplant) are 3 to 10 times more likely to get shingles than the general population. In transplant patients, shingles is often more severe. It can spread to other parts of the body and may cause long-lasting nerve pain. These problems can lower quality of life, increase doctor visits and hospital care, and may even affect how well the transplanted organ works.

The shingles vaccine called Shingrix® (recombinant zoster vaccine, RZV) works well in healthy adults and is generally safe for transplant patients. However, about 30% of transplant recipients still develop shingles even after receiving the recommended two doses. This may be because their immune system is weakened by the long-term medicines they take to prevent organ rejection.

The purpose of this clinical trial is to find out whether giving an extra (booster) dose of the shingles vaccine after transplant can improve the immune response in solid organ transplant recipients.

This study aims to answer the following questions:

• How many participants have at least twice as many shingles antibodies (anti-gE antibodies) four weeks after receiving the booster compared to before the booster?
• How strong and how long does the immune response last at 6 and 12 months?
• Is the booster dose safe for transplant patients? In this study, researchers will compare two groups: One group will receive a booster dose of the shingles vaccine. The other group will not receive the booster. They will compare the groups to see differences in immune response, cases of shingles despite vaccination, and any side effects.

Participants in the study will:

• Be randomly assigned (by chance) in a 2:1 ratio to either receive the booster or not.
• Have blood samples taken at the first visit, and again at 1 month, 6 months, and 12 months to measure antibody levels and immune responses.
• Be monitored for any possible side effects.
• Have their medical records reviewed for health events such as side effects or organ rejection.

Study Overview

• Status: Not yet recruiting
• Conditions: Zoster; Herpes
• Intervention / Treatment: Biological: Booster dose of the recombinant zoster vaccine (RZV, Shingrix®)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Oriol Manuel, MD; Phone Number: +41 79 556 61 36; Email: oriol.manuel@chuv.ch
• Study Contact Backup: Name: Elise Pickavance, MSc; Phone Number: +41 79 556 33 86; Email: elise.pickavance@chuv.ch

Study Locations

• Switzerland
  • Canton of Vaud
    • Lausanne, Canton of Vaud, Switzerland, 1011
      • Lausanne University Hospital
      • Contact: Elise Pickavance, MSc; Phone Number: +41 79 556 3386; Email: elise.pickavance@chuv.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control (no booster); Control participants will not receive an injection but will undergo blood sampling at the same time points as the experimental group - baseline (pre-randomization), and at 1, 6 and 12 months - to ensure comparability of immunological data. They will continue standard post-transplant care and routine clinical follow-up according to institutional practice.
Experimental: RZV booster; The intervention group will receive a RZV booster dose. Vaccine reconstitution will follow the manufacturer's instructions immediately before injection. Administration will be performed by a trained study nurse or investigator under medical supervision. Participants will be observed for at least 15 minutes post-injection to detect any immediate hypersensitivity or vasovagal reaction. No deviation from the commercial formulation or packaging is expected. The IMP used in this trial is identical to the marketed product authorized in Switzerland and the EU.	Biological: Booster dose of the recombinant zoster vaccine (RZV, Shingrix®); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with ≥2-fold increase in anti-gE antibody titers from baseline	The primary outcome of this study is the humoral immune response 4 weeks after the booster dose of RZV. This will be defined as the proportion of participants achieving at least a two-fold increase in anti-gE antibody titers compared with baseline levels, measured by anti-gE ELISA.	4 weeks after booster dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of VZV-specific CD4+ T-cells, (as % of total CD4+ T-cells)	Magnitude and frequency of VZV-specific CD4+ T-cell responses at 1, 6, and 12 months post-vaccination, measured by flow cytometry	4 weeks, 6 months and 12 months after booster dose
Geometric mean anti-gE antibody titers	Geometric mean titers (GMT) at 6 and 12 months post-vaccination, including pre- and post-transplantation changes.	6 and 12 months after booster dose
Incidence of confirmed herpes zoster cases	Clinically diagnosed zoster cases, preferably PCR-confirmed, via medical record review.	Through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with vaccine-related treatment-emergent adverse events, graded according to CTCAE v4.0	Local and systemic solicited adverse events following vaccination, documented in medical records and graded according to CTCAE v4.0 where applicable.	From baseline to 4 weeks after the booster dose.
Number of participants with serious adverse events and episodes of graft rejection, graded according to CTCAE v4.0 where applicable	Serious adverse events and episodes of graft rejection, documented in medical records and graded according to CTCAE v4.0 where applicable.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Oriol Manuel
• Investigators: Principal Investigator: Oriol Manuel, MD, Service des maladies infectieuses, Centre hospitalier universitaire vaudois (CHUV)

Publications and helpful links

General Publications

• Vink P, Ramon Torrell JM, Sanchez Fructuoso A, Kim SJ, Kim SI, Zaltzman J, Ortiz F, Campistol Plana JM, Fernandez Rodriguez AM, Rebollo Rodrigo H, Campins Marti M, Perez R, Gonzalez Roncero FM, Kumar D, Chiang YJ, Doucette K, Pipeleers L, Aguera Morales ML, Rodriguez-Ferrero ML, Secchi A, McNeil SA, Campora L, Di Paolo E, El Idrissi M, Lopez-Fauqued M, Salaun B, Heineman TC, Oostvogels L; Z-041 Study Group. Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial. Clin Infect Dis. 2020 Jan 2;70(2):181-190. doi: 10.1093/cid/ciz177.
• Bastidas A, de la Serna J, El Idrissi M, Oostvogels L, Quittet P, Lopez-Jimenez J, Vural F, Pohlreich D, Zuckerman T, Issa NC, Gaidano G, Lee JJ, Abhyankar S, Solano C, Perez de Oteyza J, Satlin MJ, Schwartz S, Campins M, Rocci A, Vallejo Llamas C, Lee DG, Tan SM, Johnston AM, Grigg A, Boeckh MJ, Campora L, Lopez-Fauqued M, Heineman TC, Stadtmauer EA, Sullivan KM; ZOE-HSCT Study Group Collaborators. Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial. JAMA. 2019 Jul 9;322(2):123-133. doi: 10.1001/jama.2019.9053.
• Martin-Gandul C, Stampf S, Hequet D, Mueller NJ, Cusini A, van Delden C, Khanna N, Boggian K, Hirzel C, Soccal P, Hirsch HH, Pascual M, Meylan P, Manuel O; Swiss Transplant Cohort Study (STCS). Preventive Strategies Against Cytomegalovirus and Incidence of alpha-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study. Am J Transplant. 2017 Jul;17(7):1813-1822. doi: 10.1111/ajt.14192. Epub 2017 Feb 2.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: February 13, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Solid Organ Transplant (SOT) Recipients; recombinant zoster vaccine
• Additional Relevant MeSH Terms: Varicella Zoster Virus Infection; Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Chickenpox
• Other Study ID Numbers: ZEST

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the study is completed, de-identified individual participant data may be shared. Data will be made available only after a formal request to the Principal Investigator (PI) and approval by the study's Scientific Committee. Data sharing will be limited to use for scientific research purposes and will follow all applicable privacy and ethical regulations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No