학술논문
Th1 -dominant cytokine responses in kidney patients after COVID-19 vaccination are associated with poor humoral responses
Document Type
Original Paper
Author
den Hartog, Yvette; Malahe, S. Reshwan K.; Rietdijk, Wim J. R.; Dieterich, Marjolein; Gommers, Lennert; Geers, Daryl; Bogers, Susanne; van Baarle, Debbie; Diavatopoulos, Dimitri A.; Messchendorp, A. Lianne; van der Molen, Renate G.; Remmerswaal, Ester B. M.; Bemelman, Frederike J.; Gansevoort, Ron T.; Hilbrands, Luuk B.; Sanders, Jan-Stephan; GeurtsvanKessel, Corine H.; Kho, Marcia M. L.; Reinders, Marlies E. J.; de Vries, Rory D.; Baan, Carla C.
Source
npj Vaccines. 8(1)
Subject
Language
English
ISSN
2059-0105
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.