Class switching toward IgG4 six months after primary mRNA-based COVID-19 vaccination in kidney patients
Sophie C. Frölke, Kenney G. Amirkhan, Nelly van der Bom-Baylon, Marit van Gils, Mathieu Claireaux, Suzanne E. Geerlings, Rory D. de Vries, Jan-Stephan F. Sanders, Luuk B. Hilbrands, Dimitri A. Diavatopoulos, A. Lianne Messchendorp, Michiel C. van Aalderen, Ester B. M. Remmerswaal, Frederike J. Bemelman
Abstract
Background
Class switching toward spike (S)-binding IgG4 antibodies after mRNA-based COVID-19 vaccination has been observed, an antibody subclass with strong neutralizing but limited effector activity.
Introduction
End-stage renal disease (ESRD) is associated with accelerated immune senescence and chronic inflammation, rendering patients immunocompromised [1]. COVID-19 vaccination induces protective antibodies in this population, but immunogenicity is reduced compared to controls [2], necessitating booster doses to counter declining antibody levels and emerging viral variants.
Materials and method
This study was performed in participants of the RECOVAC Immune Response (IR) study, conducted between February 1 and May 31, 2021, who visited the outpatient clinic of Amsterdam UMC in the Netherlands. The design and results of the RECOVAC-IR study have been published previously [2,18].
Results
S-binding B cells are detectable in KTRs, HD/PD, and CKD patients
First, we analyzed S1-specific IgG antibody responses. All participants were seronegative at baseline and seropositive after vaccination, as per the inclusion criteria. As expected, overall antibody levels declined between 28 days and 6 months post-vaccination: from a median of 1575 BAU/mL (IQR 616.5–3386) at V3 to 237.9 BAU/mL (IQR 105.8–492.7) at V4 (p < 0.001, r = –0.78) (Fig 1a) [2,23].
Discussion
In this study, we provide exploratory evidence suggesting that IgG4 class switching can occur after a two-dose mRNA-1273 regimen, including in KTRs under immunosuppression. Nearly half of KTRs lacked detectable S-binding B cells after vaccination, despite antibody formation. However, S-binding responders showed durable B-cell responses, including memory B-cell expansion and plasmablast formation, comparable to those in dialysis patients, CKD patients, and controls.
Acknowledgments
We would like to thank T. Standaar and I. Moerman (Amsterdam UMC location University of Amsterdam, Renal Transplant Unit, Meibergdreef 9, Amsterdam, the Netherlands) for their help with participant enrollment, and T. Dekker (Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection & Immunity, Meibergdreef 9, Amsterdam, the Netherlands) for her help with running the Biobank Renal Diseases of the Amsterdam UMC location AMC.
Citation: Frölke SC, Amirkhan KG, van der Bom-Baylon N, van Gils M, Claireaux M, Geerlings SE, et al. (2026) Class switching toward IgG4 six months after primary mRNA-based COVID-19 vaccination in kidney patients. PLoS One 21(3): e0336320. https://doi.org/10.1371/journal.pone.0336320
Editor: Maria Lourdes Gonzalez Suarez, Mayo Clinic Rochester, UNITED STATES OF AMERIC
Received: November 2, 2025; Accepted: February 9, 2026; Published: March 3, 2026
Copyright: © 2026 Frölke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting information files.
Funding: This study is funded by The Netherlands Organization for Health Research and Development (ZonMw), project number: 10430072010002. This organization had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
