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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Kidney Transplanted patients | Kidney transplanted patients transplanted at least 6 months prior to SARS-CoV-2 vaccination. Vaccination according to national plan with messenger Ribonucleic acid (mRNA) vaccine |
| |
| Healthy controls | Healthy hospital staff receiving SARS-CoV-2 mRNA vaccine as being front line Healthcare workers. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SARS-CoV-2 vaccine | Drug | SARS-CoV-2 vaccines currently on market, i.e. Pfizer/BioNTech and Moderna |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cellular immunological response | IgG antibodies against SARS-CoV-2 spike protein above assay limit of positive sample. | 1.5 months |
| Humoral immunological response | T-cell reactivity against SARS-CoV-2 spike protein, including known mutation in the spike protein. | 1.5 months |
| Measure | Description | Time Frame |
|---|---|---|
| Vaccine related side effects | Adverse drug reactions that have a reasonable relation to the vaccination, as assessed by the investigator | 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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Adult, standard risk kidney transplanted patients on tacrolimus based immunosuppressive therapy are eligible for inclusion in the project.
Adult, healthy Oslo university hospital (OUS) employees that receive vaccine as first line health care workers and that are not treated for any disease known to be a risk factor for severe COVID-19. These will be invited to participate via study information posted in the relevant clinics.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oslo University Hospital | Oslo | 0424 | Norway |
Potential sharing of de-identified immunological data. Need specific ethical Committee approval for sharing
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| ID | Term |
|---|---|
| D045169 | Severe Acute Respiratory Syndrome |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
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| ID | Term |
|---|---|
| D000086663 | COVID-19 Vaccines |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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Whole blood Serum Isolated blood cells DNA
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |