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The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees.

Department of Experimental Immunohematology, Sanquin Research, Amsterdam, the Netherlands; Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, the Netherlands. Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands. Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany; Department of Anesthesiology and Intensive Care, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany. Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam UMC, University of Amsterdam, the Netherlands. Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam, the Netherlands. Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam, the Netherlands; Department of Intensive Care, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany. Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, the Netherlands; Department of Immunopathology, Sanquin Research, Amsterdam, the Netherlands. Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Rheumatology and Clinical Immunology, Amsterdam UMC, Amsterdam Rheumatology and Immunology Center, Amsterdam, the Netherlands. Medical Department 2, University Heart Center of Schleswig-Holstein, Lübeck, Germany. Amsterdam UMC Biobank, Amsterdam UMC, Amsterdam, the Netherlands. Department of Internal Medicine, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands. Department of Intensive Care, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: M.wuhrer@lumc.nl. Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany; Airway Research Center North, University of Lübeck, German Center for Lung Research (DZL), Lübeck, Germany. Electronic address: Marc.ehlers@uksh.de. Department of Experimental Immunohematology, Sanquin Research, Amsterdam, the Netherlands; Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, the Netherlands. Electronic address: G.Vidarsson@sanquin.nl.

EBioMedicine. 2023;:104408
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Abstract

BACKGROUND Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced FcγRIIIa binding, can also trigger exacerbated pro-inflammatory responses in severe COVID-19. We investigated if the BNT162b2 SARS-CoV-2 mRNA also induced afucosylated IgG responses. METHODS Blood from vaccinees during the first vaccination wave was collected. Liquid chromatography-Mass spectrometry (LC-MS) was used to study anti-S IgG1 Fc glycoprofiles. Responsiveness of alveolar-like macrophages to produce proinflammatory cytokines in presence of sera and antigen was tested. Antigen-specific B cells were characterized and glycosyltransferase levels were investigated by Fluorescence-Activated Cell Sorting (FACS). FINDINGS Initial transient afucosylated anti-S IgG1 responses were found in naive vaccinees, but not in antigen-experienced ones. All vaccinees had increased galactosylated and sialylated anti-S IgG1. Both naive and antigen-experienced vaccinees showed relatively low macrophage activation potential, as expected, due to the low antibody levels for naive individuals with afucosylated IgG1, and low afucosylation levels for antigen-experienced individuals with high levels of anti-S. Afucosylation levels correlated with FUT8 expression in antigen-specific plasma cells in naive individuals. Interestingly, low fucosylation of anti-S IgG1 upon seroconversion correlated with high anti-S IgG levels after the second dose. INTERPRETATION Here, we show that BNT162b2 mRNA vaccination induces transient afucosylated anti-S IgG1 responses in naive individuals. This observation warrants further studies to elucidate the clinical context in which potent afucosylated responses would be preferred. FUNDING LSBR1721, 1908; ZonMW10430012010021, 09150161910033, 10430012010008; DFG398859914, 400912066, 390884018; PMI; DOI4-Nr. 3; H2020-MSCA-ITN 721815.