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.
