T-cell cytokine profiles after mRNA-1273 COVID-19 vaccination in kidney patients
Yvette den Hartog 1, Reshwan S.R.K. Malahe1, Marjolein Dieterich 1, Daryl Geers2, Marcia M.L. Kho1, Rory D de Vries 2, Marlies E.J. Reinders1, Carla C. Baan1.
1Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, Rotterdam, Netherlands; 2Viroscience, Medical Center Rotterdam, Rotterdam, Netherlands
RECOVAC.
Background: T-cells are fundamental in the control and clearance of viral infections and contribute to protective immunity by long-term immunological memory. The mRNA-1273 COVID-19 (Moderna) vaccine induces durable SARS-CoV-2 Spike (S) specific CD4+ and CD8+ T-cell responses. However, little is known about the phenotype of these S-specific T-cells over time in kidney patients with a potentially disturbed immune system. Here, we investigated the cytokines produced by T-cells obtained from mRNA-1273 vaccinated kidney patients after ex vivo stimulation.
Methods: Patients on dialysis (n=38), with chronic kidney disease (CKD, n=37), kidney transplant recipients (n=67) and controls (n=42) were vaccinated twice with the mRNA-1273 COVID-19 vaccine. Whole blood obtained pre-vaccination, and 28 days and six months after second vaccination, was stimulated with peptides covering the S protein in a commercially available IFN-γ release assay (QuantiFERON, QIAGEN). After stimulation, cytokines (IL-2, 4, 5, 6, 9, 10, 13, 17A, 17F, 22, IFN-γ and TNF-α) were measured in plasma by a multiplex bead assay and ELISA (IL-21). Patients were clustered at 28-days after second vaccination to identify cytokine production profiles via unsupervised clustering.
Results: After ex vivo stimulation with peptides covering the S protein a specific IFN-γ, IL-2, IL-5, and IL-13 response was found in all cohorts. Particularly, the Th1 cytokines (IFN-γ, IL-2) could still be detected six months after vaccination. Clustering analysis revealed no difference in cytokine profile between kidney patients and controls. Cytokine production was significantly lower in kidney transplant recipients compared to the other cohorts at 28 days and six months after vaccination (p<0.01). However, S-specific T-cell responses were still detectable in 79% of kidney transplant recipients based on the production of IL-2.
Conclusion: Our study shows that after mRNA-1273 COVID-19 vaccination, kidney transplant recipients have fewer S-specific T-cells, based on a multiplex cytokine assay. However, we were able to detect cytokines produced by SARS-CoV-2-specific T-cells even after six months in 79% of the kidney transplant recipients.
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