Shingrix in Renal Transplant Recipients

Overview

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.

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.