None of the vaccines approved, or in clinical trials, have so far been tested on transplanted patients. If they produce an immune response to the Spike protein of SARS-CoV-2 it is unknown how long the protective immunity will last. Not all immune responses are equal. The investigators will quantify immune cell subsets with flow and mass cytometry analyses to describe the phenotype of responding immune cells, including specific T cells. If not already established, patient human Leukocyte antigen (HLA) genotypes will be typed. In order to compare the immune responses with healthy individuals a control group of hospital employees will be included and sampled before and after vaccination according to the same time schedules as the kidney transplanted patients.
Kidney transplanted patients with post-transplant follow-up visits at the national transplant
center in Norway will be included before they are SARS-CoV-2 vaccinated. As a control group
the investigators will include blood samples from healthy volunteers (hospital employees)
that receive vaccine as first line health care workers.
Baseline blood samples will be obtained before vaccination. The vaccination will be performed
according to the national procedures and not necessarily by the hospital. Following
vaccination, all patients and controls will have blood drawn 7-10 days as well as 4-6 weeks
after the second dose. Depending on the results of the immunity testing the patients and
controls may be invited to additional blood sampling up or at specific time points to two
years following vaccination.
At each blood sampling and at the time of both vaccinations the systemic exposure of
tacrolimus will be assessed in kidney transplanted patients.
All samples will be analyzed with validated assays for SARS-CoV-2 immunoglobulin G (IgG)
(anti-receptor binding domain (RBD) spike protein) using ELISA, flow cytometry bead arrays
and SARS-CoV-2 neutralization assays or comparable techniques. Cells will be analyzed by flow
and mass cytometry for activation and phenotype markers, and with functional assays for
responsiveness (e.g. proliferation and cytokine production). Samples will be HLA-typed if
HLA-genotype if not already established.
Drug: SARS-CoV-2 vaccine
SARS-CoV-2 vaccines currently on market, i.e. Pfizer/BioNTech and Moderna
Inclusion Criteria:
- Patients transplanted with a kidney (only) at least 6 months before vaccination OR
healthy volunteer first line health care workers at OUS.
- Age of 18 years or older (also for controls).
- Standard immunological risk at transplantation (i.e. no donor specific HLA antibodies
(DSA)) and not performed an ABO blood-type-incompatible transplantation.
- No treatment for rejection episodes the last 6 months before inclusion.
- Immunosuppressive therapy including tacrolimus, mycophenolate and prednisolone.
- Stable graft-function the last 6 months.
- S-creatinine < 200 μmol/L (also for controls).
- Signed informed consent to participate in the study (also for controls).
Exclusion Criteria:
- Three or more previous transplantations.
- Hemoglobin level below 10 g/dL (also for control).
- Leukopenia defined as total lymphocyte count < 2 X 109 (also for controls).
- Previous treatment with anti-thymocyte antibodies (ATG) or rituximab.
Oslo University Hospital
Oslo, Norway