Shingrix in Renal Transplant Recipients
brief summary
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.
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.
official title
Safety and Immunogenicity of Shingrix in Renal Transplant Recipients