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Th 1 -dominant cytokine responses in kidney patients after COVID-19 vaccination are associated with poor humoral responses.

Authors :
den Hartog Y
Malahe SRK
Rietdijk WJR
Dieterich M
Gommers L
Geers D
Bogers S
van Baarle D
Diavatopoulos DA
Messchendorp AL
van der Molen RG
Remmerswaal EBM
Bemelman FJ
Gansevoort RT
Hilbrands LB
Sanders JS
GeurtsvanKessel CH
Kho MML
Reinders MEJ
de Vries RD
Baan CC
Source :
NPJ vaccines [NPJ Vaccines] 2023 May 17; Vol. 8 (1), pp. 70. Date of Electronic Publication: 2023 May 17.
Publication Year :
2023

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 <superscript>+</superscript> and CD8 <superscript>+</superscript> 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) <subscript>1</subscript> (IL-2, TNF-α, and IFN-γ) and Th <subscript>2</subscript> (IL-4, IL-5, IL-13) cytokines, and low levels of Th <subscript>17</subscript> (IL-17A, IL-22) and Th <subscript>9</subscript> (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 Th <subscript>1</subscript> cytokines upon re-stimulation, with lower levels or absence of Th <subscript>2</subscript> , Th <subscript>17</subscript> , and Th <subscript>9</subscript> cytokines. Multivariate analyses indicated that a balanced memory T cell response with the production of Th <subscript>1</subscript> and Th <subscript>2</subscript> 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.<br /> (© 2023. The Author(s).)

Details

Language :
English
ISSN :
2059-0105
Volume :
8
Issue :
1
Database :
MEDLINE
Journal :
NPJ vaccines
Publication Type :
Academic Journal
Accession number :
37198189
Full Text :
https://doi.org/10.1038/s41541-023-00664-4