Th1-dominant cytokine responses in kidney patients after COVID-19 vaccination are associated with poor humoral responses

Yvette den Hartog, S Reshwan K Malahe, RECOVAC Consortium / RECOVAC Collaborators, Wim J R Rietdijk, Marjolein Dieterich, Lennert Gommers, Daryl Geers, Susanne Bogers, Debbie van Baarle, Dimitri A Diavatopoulos, A Lianne Messchendorp, Renate G van der Molen, Ester B M Remmerswaal, Frederike J Bemelman, Ron T Gansevoort, Luuk B Hilbrands, Jan-Stephan Sanders, Corine H GeurtsvanKessel, Marcia M L Kho, Marlies E J ReindersRory D de Vries, Carla C Baan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Cytokines are regulators of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the contribution of cytokine-secreting CD4+ and CD8+ memory T cells to the SARS-CoV-2-specific humoral immune response in immunocompromised kidney patients is unknown. Here, we profiled 12 cytokines after stimulation of whole blood obtained 28 days post second 100 μg mRNA-1273 vaccination with peptides covering the SARS-CoV-2 spike (S)-protein from patients with chronic kidney disease (CKD) stage 4/5, on dialysis, kidney transplant recipients (KTR), and healthy controls. Unsupervised hierarchical clustering analysis revealed two distinct vaccine-induced cytokine profiles. The first profile was characterized by high levels of T-helper (Th)1 (IL-2, TNF-α, and IFN-γ) and Th2 (IL-4, IL-5, IL-13) cytokines, and low levels of Th17 (IL-17A, IL-22) and Th9 (IL-9) cytokines. This cluster was dominated by patients with CKD, on dialysis, and healthy controls. In contrast, the second cytokine profile contained predominantly KTRs producing mainly Th1 cytokines upon re-stimulation, with lower levels or absence of Th2, Th17, and Th9 cytokines. Multivariate analyses indicated that a balanced memory T cell response with the production of Th1 and Th2 cytokines was associated with high levels of S1-specific binding and neutralizing antibodies mainly at 6 months after second vaccination. In conclusion, seroconversion is associated with the balanced production of cytokines by memory T cells. This emphasizes the importance of measuring multiple T cell cytokines to understand their influence on seroconversion and potentially gain more information about the protection induced by vaccine-induced memory T cells.

Original languageEnglish
Article number70
Journalnpj Vaccines
Volume8
Issue number1
DOIs
Publication statusPublished - 17 May 2023

Bibliographical note

Acknowledgements
We would like to thank BernArt Visuals for designing the graphical abstract.Next to this, we would like to thank all participants of the RECOVAC study. This research was funded by the Netherlands Organization for Health Research and Development (ZonMw), project number: 10430072010002. This study was also supported by the Dutch Kidney Foundation (project 21OP + 036 and CP1801). Both organizations had no role in the design of the study, data interpretation, writing of the manuscript, nor in the decision to submit the manuscript.

© 2023. The Author(s).

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