# Class switching toward IgG4 six months after primary mRNA-based COVID-19 vaccination in kidney patients

## TL;DR

The study found that kidney patients showed a shift toward IgG4 antibodies six months after receiving an mRNA-based COVID-19 vaccine, similar to healthy individuals.

## Contribution

This is the first study to explore IgG subclass dynamics in kidney patients after mRNA vaccination, revealing a relative shift toward IgG4.

## Key findings

- Approximately half of kidney transplant recipients lacked detectable S-binding B cells after two vaccine doses.
- S-binding B cells persisted up to six months with a relative shift toward IgG4 in all groups.
- The IgG4:IgG1 log-ratio increased significantly from 28 days to six months post-vaccination.

## Abstract

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. While this has been reported in healthy individuals, subclass dynamics in immunocompromised kidney patients are unclear. We assessed IgG subclass patterns and S-specific B-cell phenotypes up to 6 months after a two-dose mRNA-1273 vaccination schedule in kidney transplant recipients (KTRs), dialysis patients, and patients with chronic kidney disease (CKD).

In this exploratory study, KTRs (n = 11), dialysis patients (n = 5), CKD stage G4–5 patients (eGFR < 30 ml/min/1.73m2, n = 5), and controls without known kidney disease (eGFR > 45 ml/min/1.73m2, n = 8) received two mRNA-1273 doses 28 days apart. Blood was collected pre-vaccination (V1), and at 28 days (V3) and 6 months (V4) after the second dose. S1-specific IgG antibodies were measured by a validated fluorescent bead-based multiplex-immunoassay, and participants seronegative at V1 and seropositive at V3 were included. B cells were phenotyped by flow cytometry.

Five of 11 KTRs had no detectable S-binding B cells, whereas all other groups mounted responses. Across responders, the frequency of S-binding B cells increased from V1 (median 0.08%) to 0.49% at V3 and to 0.84% at V4 (both p < 0.0001). S-binding B cells mainly comprised IgG⁺ plasmablasts. The IgG4:IgG1 log-ratio increased significantly from V3 to V4 (p < 0.001), indicating a relative shift toward IgG4; absolute frequencies were comparable across the groups.

Approximately half of KTRs lacked detectable S-binding B cells after two mRNA-1273 doses, despite antibody formation. Among responders, S-binding B cells persisted up to 6 months after vaccination with a relative shift toward IgG4, a pattern also observed in dialysis patients, CKD patients and controls. The clinical significance of this subclass skewing requires confirmation in larger cohorts with functional antibody readouts.