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.
None
None
Parallel
Shingrix
Biological/VaccineIntervention: 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
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)
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.
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.
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.
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.
Safety and Reactogenicity of Shingrix
Incidence and severity of adverse events following vaccination, including local and systemic reactions.
Changes in Calculated Panel-Reactive Antibodies (cPRA)
Changes in cPRA levels before and after vaccination to assess potential effects on transplant immunologic sensitization.
Humoral Immune Response (Antibody Levels)
gE-specific antibody responses measured by gpELISA and their kinetics over time.
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.
Click on the lead sponsor to view all of their trials.
University of Colorado, Denver
Lead sponsor
GlaxoSmithKline
Collaborator
