Shingrix in Renal Transplant Recipients

Safety and Immunogenicity of Shingrix in Renal Transplant Recipients

The goal of this clinical trial is to learn how well the shingles vaccine (Shingrix) works and how safe it is in adults with kidney failure who are waiting for a kidney transplant, including those who later receive a transplant. The study also aims to find out whether giving an extra (third) dose of the vaccine after transplant improves protection.

The main questions it aims to answer are:

How strong is the body's immune response to the vaccine at different time points (about 1 month, 2 years, and 3 years after vaccination) in people waiting for a kidney transplant?

Does a third dose of the vaccine after transplant improve the immune response compared to not receiving a third dose?

How long does protection from the vaccine last before and after transplant?

How safe is the vaccine in this group, including whether it affects transplant-related immune markers?

Researchers will compare people who receive a third dose of the vaccine after transplant to those who do not receive a third dose, as well as to results from similar groups studied in the past, to see if the extra dose improves immune protection.

Participants will:

Be screened to see if they can take part in the study Attend about 3 to 6 study visits over approximately 30 to 37 months Receive two doses of the shingles vaccine if they have not already been vaccinated, or complete study assessments if they were vaccinated before joining

If they receive a kidney transplant during the study, be randomly assigned (by chance) to receive either a third dose of the vaccine or no additional dose

Complete questionnaires, have physical exams if needed, and provide blood (and urine, if applicable) samples at study visits

Take part in follow-up visits to check immune response and safety, with the option to allow samples to be stored for future research

Shingrix is approved for adults aged 50 and older and for younger adults with weakened immune systems. However, giving a third dose after a kidney transplant is not standard practice and is being studied in this trial.

Study Overview

• Status: Recruiting
• Conditions: Kidney Failure, Chronic; Kidney Transplantation; Kidney Failure; Kidney Transplant Recipient Response to Shingrix Vaccine; Herpes Zoster (HZ)
• Intervention / Treatment: Biological: Shingrix

Detailed Description

This study is designed to evaluate the immunogenicity and safety of the adjuvanted recombinant glycoprotein E (gE) herpes zoster (HZ) vaccine (Shingrix) in adults with renal failure, including those who subsequently undergo kidney transplantation. Patients with chronic renal failure and transplant recipients have impaired cellular immunity due to underlying disease and immunosuppressive therapy, placing them at increased risk for herpes zoster and related complications, including post-herpetic neuralgia and disseminated varicella-zoster virus infection. Although Shingrix is recommended for immunocompromised adults, the magnitude, durability, and optimal timing of immune responses in the setting of renal failure and transplantation remain incompletely defined.

The primary objective is to determine whether Shingrix induces acceptable cellular immune responses, as measured by gE-specific T cell activity using FluoroSpot assays, and to evaluate the safety of vaccination in this population. Vaccine response (VR) is defined as a ≥2-fold increase in gE-specific IL-2 FluoroSpot responses compared to baseline, and geometric mean fold rise (GMFR) will be used to quantify the magnitude of immune responses.

Among renal transplant candidates vaccinated at study entry, the study will assess whether ≥60% achieve a vaccine response at 30 days after the second dose and whether the GMFR is at least 60% of that observed in historical immunocompetent controls. In participants who completed the two-dose Shingrix series prior to enrollment, immune response magnitude will be compared with historical controls, adjusted for time since vaccination.

For participants who undergo kidney transplantation, the study will evaluate immune responses before and after transplantation and assess the effect of a third (booster) dose of Shingrix administered post-transplant. Transplant recipients who receive a third dose will be compared with those who do not receive a third dose, with the primary comparison focused on gE-specific cellular immune responses at 1 year after transplantation. Additional comparisons will include responses at ≥2 months post-transplant and 30 days after the third dose, as well as comparisons with non-transplanted participants and historical controls following standard two-dose vaccination.

Safety will be evaluated throughout the study, including assessment of adverse events and monitoring of transplant-related immunologic parameters such as calculated panel-reactive antibodies (cPRA). The study will also assess the overall safety profile of Shingrix administered before and/or after transplantation.

The study is designed to address key gaps in knowledge regarding optimal vaccination strategies in transplant populations. Two approaches are evaluated: vaccination prior to transplantation, when immune competence may be greater, and a combined strategy of pre-transplant vaccination followed by post-transplant boosting. Pre-transplant vaccination may provide early protection during the high-risk post-transplant period and may induce more robust immune memory prior to the initiation of intensive immunosuppression.

Herpes zoster represents a significant clinical and economic burden in transplant recipients, with reported incidence rates of approximately 1.9 cases per 100 patient-years in solid organ transplant populations and substantial associated healthcare costs. Optimizing the use of Shingrix in this population has the potential to reduce morbidity and improve outcomes in patients with renal failure and those undergoing transplantation.

Immunologic outcomes will include measurement of both humoral and cellular immune responses, including gE-specific antibody levels and T cell responses. Cellular immunity will be assessed using validated FluoroSpot assays measuring IL-2-producing cells, with additional exploratory analyses of T cell subsets (including central memory, effector memory, follicular helper, and stem cell memory T cells) to better characterize immune durability and function. Peripheral blood mononuclear cells will be processed and analyzed using standardized procedures to ensure reproducibility and comparability with historical datasets.

Overall, this study will define the magnitude and durability of immune responses to Shingrix in patients with renal failure, determine the impact of kidney transplantation on vaccine-induced immunity, and evaluate whether a third dose administered after transplantation enhances immune protection. These findings are expected to inform vaccination strategies for transplant candidates and recipients and address an important unmet need in immunocompromised populations.

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tori Rutherford, RN BSN; Phone Number: 303-724-2454; Email: tori.rutherford@childrenscolorado.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz
      • Contact: Tori Rutherford, RN BSN; Phone Number: 303-724-2454; Email: tori.rutherford@childrenscolorado.org
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Varun K Phadke, MD; Email: varun.phadke@emory.edu
      • Principal Investigator: Varun K Phadke, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Amy C Sherman, MD; Email: acsherman@bwh.harvard.edu
      • Principal Investigator: Amy C Sherman, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Contact: Hana ElSahly, MD; Email: Hana.ElSahly@bcm.edu
      • Principal Investigator: Hana ElSahly, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Study Population:

Adults with chronic kidney failure who are listed for kidney transplantation at participating transplant centers.

Inclusion Criteria:

Age 18 to 70 years Able and willing to provide written informed consent Currently on the waiting list for kidney transplantation at a participating institution, with anticipated transplantation occurring between >3 and 24 months after the first dose of Shingrix

Either:

Eligible to receive Shingrix at study entry per CDC-recommended schedule, or Previously completed the Shingrix vaccination series within 3 to 24 months prior to study entry Female participants of non-childbearing potential (e.g., tubal ligation, hysterectomy, ovariectomy, or post-menopausal ≥12 months)

Female participants of childbearing potential must:

Use adequate contraception for at least 30 days prior to vaccination Have a negative pregnancy test on the day of each vaccination Agree to continue adequate contraception during the study and for 2 months after completing the vaccination series Be considered by the investigator likely to comply with study requirements

Exclusion Criteria:

Active immunosuppressive or immunodeficient condition (e.g., malignancy, HIV infection) or receipt of immunosuppressive therapy within 3 months prior to planned vaccination that, in the investigator's opinion, may interfere with vaccine response History of herpes zoster (shingles) within the past 3 years Receipt of varicella vaccine within 3 years prior to study entry Known allergy to any component of the Shingrix vaccine Receipt of investigational drugs within 30 days prior to enrollment or planned use during the study Receipt of non-live vaccines within 2 weeks prior to any Shingrix dose or planned within 30 days after vaccination Receipt of live vaccines within 4 weeks prior to any Shingrix dose or planned within 30 days after vaccination Pregnant or breastfeeding Planned or prior multi-organ transplantation Residence or travel distance greater than 2 hours from the study site, which would interfere with study visits or timely processing of blood samples

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transplanted subject; Experimental Arm: Third Dose of Shingrix (Post-Transplant) Participants who undergo kidney transplantation within 24 months after initial vaccination will be randomized to receive a third (booster) dose of the recombinant zoster vaccine (Shingrix) after transplantation. These participants will be followed to assess immunogenicity (e.g., vaccine response and geometric mean fold rise) and safety outcomes over time.	Biological: Shingrix; Intervention: Biological - Recombinant Zoster Vaccine (Shingrix) The recombinant adjuvanted glycoprotein E (gE) herpes zoster vaccine (Shingrix) will be administered as a 0.5 mL intramuscular injection per dose. Participants who have not previously received Shingrix will receive the standard two-dose series, with doses administered at Month 0 and Month 2. Participants who have previously completed the primary two-dose series will not receive additional doses at study entry. Participants who undergo kidney transplantation within 24 months after initial vaccination will be randomized to receive either a third (booster) dose of Shingrix or no additional dose. The third dose, when administered, will consist of a single 0.5 mL intramuscular injection given at least 2 months following transplantation, when clinically stable. The duration of participation for vaccination and follow-up is approximately 30 to 37 months. Immunogenicity and safety outcomes will be assessed at multiple time points
No Intervention: No Intervention Comparator Arm: No Third Dose (Post-Transplant); Participants who undergo kidney transplantation within 24 months after initial vaccination will be randomized to receive no additional (third) dose of Shingrix after transplantation. These participants will undergo the same follow-up assessments to evaluate immunogenicity and safety outcomes and will serve as the comparator group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gE-Specific IL-2 T Cell Response at 12 Months After Randomization	1. gE-Specific IL-2 T Cell Response at 12 Months After Randomization Description: Cellular immune response measured by gE-specific IL-2-producing spot-forming cells (SFC) per 10⁶ peripheral blood mononuclear cells (PBMC) using FluoroSpot assay in renal transplant recipients. Comparison between participants who receive a third dose of Shingrix post-transplant and those who do not receive a third dose. Time frame: 12 months after vaccination (post-transplant)	12 months after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine Response (VR) at 30 Days After Second Dose	Description: Proportion of participants achieving a ≥2-fold increase in gE-specific IL-2 FluoroSpot responses compared to pre-vaccination baseline among transplant candidates vaccinated at study entry.	Time Frame: 30 days after second dose (approximately Month 3)
Geometric Mean Fold Rise (GMFR) in gE-Specific IL-2 Responses at 30 Days After Second Dose	Description: Fold increase in gE-specific IL-2 FluoroSpot responses from baseline in transplant candidates vaccinated at study entry, compared with historical controls.	Time Frame: 30 days after second dose
GMFR in Previously Vaccinated Participants	Description: Magnitude of gE-specific IL-2 FluoroSpot responses in participants who completed the two-dose Shingrix series prior to enrollment, compared with historical controls adjusted for time since vaccination.	Time Frame: Study entry, 24 months, and 36 months after vaccination
Immunogenicity at ≥2 Months Post-Transplant	Description: GMFR in gE-specific IL-2 FluoroSpot responses in transplant recipients at least 2 months after transplantation, compared with historical controls and non-transplanted participants.	Time Frame: ≥2 months post-transplant
Immune Response 30 Days After Third Dose (Post-Transplant)	VR and GMFR in transplant recipients 30 days after receipt of a third dose of Shingrix, compared with historical controls (after two doses) and non-transplanted participants.	30 days after third dose
GMFR at 1 Year Post-Randomization	Comparison of GMFR in transplant recipients who receive a third dose versus those who do not, and versus historical controls after two-dose vaccination.	12 months after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Reactogenicity of Shingrix	Incidence and severity of adverse events following vaccination, including local and systemic reactions.	Throughout study participation (up to 37 months)
Changes in Calculated Panel-Reactive Antibodies (cPRA)	Changes in cPRA levels before and after vaccination to assess potential effects on transplant immunologic sensitization.	Baseline and post-vaccination through study completion
Humoral Immune Response (Antibody Levels)	gE-specific antibody responses measured by gpELISA and their kinetics over time.	Multiple time points up to 36 months
T Cell Subset Responses	Characterization of gE-specific CD4+ T cell subsets (e.g., central memory, effector memory, T follicular helper, and stem cell memory T cells) using flow cytometry.	Selected time points during study participation

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Myron J Levin, MD, University of Colorado Anschutz School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2023
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Renal Transplantation; Chronic Kidney Disease; Immunogenicity; Herpes Zoster; Shingles; Renal Failure; Kidney Failure; Immunocompromised; Kidney Transplant; Vaccine Response; T Cell Response; Herpes Zoster Vaccine; Shingrix; Cellular Immunity; Vaccine Safety; Booster Dose; Recombinant Zoster Vaccine; Transplant Candidates; Vaccine Durability; Post-Transplant Immunity
• Additional Relevant MeSH Terms: Varicella Zoster Virus Infection; Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Herpes Zoster
• Other Study ID Numbers: 19-0005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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