Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) Immune Kidney Transplant Study (COVID-19) (SCV-KTx-imm)

SARS-CoV-2 Cellular and Humoral Immune Response Following Vaccination of Kidney Transplant Recipients and Healthy Controls

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Kidney Transplant Infection; SARS-CoV Infection
• Intervention / Treatment: Drug: SARS-CoV-2 vaccine

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.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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	Drug: SARS-CoV-2 vaccine; SARS-CoV-2 vaccines currently on market, i.e. Pfizer/BioNTech and Moderna
Healthy controls; Healthy hospital staff receiving SARS-CoV-2 mRNA vaccine as being front line Healthcare workers.	Drug: SARS-CoV-2 vaccine; SARS-CoV-2 vaccines currently on market, i.e. Pfizer/BioNTech and Moderna

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Vaccination; Humoral; Cellular
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Disease Attributes; Severe Acute Respiratory Syndrome; Infections; Communicable Diseases
• Other Study ID Numbers: 227626

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Potential sharing of de-identified immunological data. Need specific ethical Committee approval for sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes