Clinical trial NCT04747522: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) Immune Kidney Transplant Study (COVID-19)
Official title: SARS-CoV-2 Cellular and Humoral Immune Response Following Vaccination of Kidney Transplant Recipients and Healthy Controls
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Kidney Transplant Infection
SARS-CoV Infection
Keywords: Vaccination
Humoral
Cellular
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2021-02-10
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cellular immunological response
timeFrame: 1.5 months
measure: Humoral immunological response
timeFrame: 1.5 months
Secondary outcomes:
measure: Vaccine related side effects
timeFrame: 6 months
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
References: