Immunosuppression, Vaccine Response Impaired
Conditions
Brief summary
The goal of this clinical trial is to compare responses to Varicella Zoster vaccination between 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 transplant patients on different immunosuppression regimens? 2. Are there differences in vaccination immunological responses between 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.
Interventions
BIOLOGICALRecombinant zoster vaccine adjuvanted (SHINGRIX)
2 doses of 0.5mL recombinant zoster vaccine adjuvanted intramuscular injection at week 0 and week 8.
Sponsors
Central Adelaide Local Health Network Incorporated
National Health and Medical Research Council, Australia
University of Adelaide
Royal Prince Alfred Hospital, Sydney, Australia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Population - Group 1. Healthy co-habitants (n = 30) Inclusion criteria: * Household co-habitant of transplant recipient in trial * Aged \>50 years * Previous documented infection with VZV (known infection history or positive VZV IgG result)
Exclusion criteria
* Aged \<50 years * Unable or unwilling to provide informed consent to participate in the trial * Known allergy to or intolerance of the contents of the RZV vaccine * No previous infection with VZV (chickenpox) * History of primary immunodeficiency, documented vaccine hypo-responsiveness, or active immunosuppressive therapy 2. Population - Groups 2-4. Transplant recipients (n = 90) Inclusion criteria: * Organ transplant recipients \-- Specific immunosuppression regimen * Tacrolimus, mycophenolate, prednisolone (n = 30, Group 2) * Tacrolimus, mTORi, prednisolone (n = 30, Group 3) * mTORi, mycophenolate, prednisolone (n = 30, Group 4) * Aged \>18 years * estimated GFR \> 15 mL/min/1.73m2 * Previous documented infection with VZV (known infection history or positive VZV IgG result)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
| 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 |
Countries
Australia
Contacts
CONTACTPatrick T Coates, MBBS, FRACP, PhD
CONTACTGriffith B Perkins, PhD
PRINCIPAL_INVESTIGATORPatrick T Coates, FRACP
Central and Northern Adelaide Renal and Transplantation Services
Outcome results
None listed