Safety and Immunogenicity of Recombinant Zoster Vaccine for Kidney Transplant Recipients

Not Applicable

Recruiting

• Conditions: Immunosuppression; Vaccine Response Impaired
• Interventions: Biological: Recombinant zoster vaccine adjuvanted (SHINGRIX)

• Registration Number: NCT06262776
• Lead Sponsor: Central Adelaide Local Health Network Incorporated

Brief Summary

The goal of this clinical trial is to compare responses to Varicella Zoster vaccination between kidney transplant patients on different medication regimens, and their healthy co-habitants. The main questions it aims to answer are:

1. Are there differences in vaccination immunological responses in kidney transplant patients on different immunosuppression regimens?

2. Are there differences in vaccination immunological responses between kidney transplant patients and their healthy co-habitants? Participants will all receive a 2-dose course of SHINGRIX recombinant Zoster vaccination, and have immunological responses measured and compared at 5 timepoints between 1 week to 1 year post-vaccination.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-01-31
• Study First Submitted QC: 2024-02-14
• Study First Posted: 2024-02-16
• Study Start: 2024-03-20
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-10
• Last Update Posted: 2025-02-12
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Single organ kidney transplant recipient, currently receiving a specific immunosuppression regimen:

  1. Calcineurin inhibitor (tacrolimus or cyclosporine), antimetabolite (mycophenolate derivative or azathioprine), and oral steroid (n = 30)
  2. Calcineurin inhibitor (tacrolimus or cyclosporine), mTOR inhibitor (sirolimus or everolimus), and oral steroid (n = 30)
  3. mTOR inhibitor (sirolimus or everolimus), antimetabolite (mycophenolate derivative or azathioprine), and oral steroid (n = 30)

• Aged >18 years

• estimated glomerular filtration rate (GFR) > 15 mL/min/1.73m2

• Previous documented infection with Varicella zoster (known infection history or positive Varicella zoster IgG result)

OR

• Healthy household cohabitant of kidney transplant recipient enrolled in trial (n = 30)
• Aged > 50 years
• Previous documented infection with Varicella zoster (known infection history or positive Varicella zoster IgG result)

Exclusion Criteria

• Unable or unwilling to provide informed consent to participate in the trial
• No previous infection with Varicella zoster (chickenpox)
• Known allergy to or intolerance of the contents of the SHINGRIX vaccine
• Current pregnancy
• For healthy household cohabitants, history of primary immunodeficiency, documented vaccine hypo-responsiveness, or active immunosuppressive therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vaccination group	Recombinant zoster vaccine adjuvanted (SHINGRIX)	All participants will receive the assigned intervention, a 2-dose course of Zoster recombinant adjuvanted vaccine. Study participants will include kidney transplant recipients receiving specific immunosuppressive medications, and non-immunosuppressed household cohabitants, with comparisons made in magnitude of vaccine response.

Primary Outcome Measures

Name	Time	Method
Functional T cell memory	3 weeks following second vaccine dose	ELISpot measurement of interferon gamma spot-forming units following 18-hour stimulation of peripheral blood mononuclear cells with Zoster gE protein-derived peptide array

Secondary Outcome Measures

Name	Time	Method
Frequency of polyfunctional T cells	3 weeks and 52 weeks following second vaccine dose	Change in frequency of Zoster gE protein-specific polyfunctional T cells identified by flow cytometry intracellular cytokine staining (interferon-gamma, interleukin-2, tumour necrosis factor) following 24-hour stimulation with a gE protein-derived peptide array.
Frequency of virus specific T cells	3 weeks and 52 weeks following second vaccine dose	Change in frequency of CD8+ Zoster gE protein-specific T cells identified by flow cytometry as CD8+CD134+CD69+ following 24-hour stimulation with a gE protein-derived peptide array
Magnitude of antibody response	3 weeks and 52 weeks following second vaccine dose	Anti Varicella zoster gE Immunoglobulin M (IgM) and IgG antibody titres compared to baseline
Concentration of post-vaccination circulating cytokines	3 weeks following second vaccine dose	Post-vaccination circulating cytokines compared to baseline
Frequency of virus-specific T stem cell memory compared to baseline	3 weeks and 52 weeks following second vaccine dose	Frequency of Zoster gE protein-specific T stem cell memory (Tscm) will be determined by flow cytometry based on expression of T cell phenotypic markers (CD27+CD45RA+CD95+) on activation-induced marker-positive CD4 and CD8 T cells
Magnitude of vaccine-induced cross-protective antiviral responses	3 weeks and 52 weeks following second vaccine dose	T cells will be investigated for cross-protective herpesviridae responses using interferon gamma ELISpot compared to baseline following 24-hour stimulation with a gE protein-derived peptide array.

Trial Locations

Locations (1)

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia