EBioMedicine (Jan 2023)
The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccineesResearch in context
- Julie Van Coillie,
- Tamas Pongracz,
- Johann Rahmöller,
- Hung-Jen Chen,
- Chiara Elisabeth Geyer,
- Lonneke A. van Vught,
- Jana Sophia Buhre,
- Tonći Šuštić,
- Thijs Luc Junior van Osch,
- Maurice Steenhuis,
- Willianne Hoepel,
- Wenjun Wang,
- Anne Sophie Lixenfeld,
- Jan Nouta,
- Sofie Keijzer,
- Federica Linty,
- Remco Visser,
- Mads Delbo Larsen,
- Emily Lara Martin,
- Inga Künsting,
- Selina Lehrian,
- Vera von Kopylow,
- Carsten Kern,
- Hanna Bele Lunding,
- Menno de Winther,
- Niels van Mourik,
- Theo Rispens,
- Tobias Graf,
- Marleen Adriana Slim,
- René Peter Minnaar,
- Marije Kristianne Bomers,
- Jonne Jochum Sikkens,
- Alexander P.J. Vlaar,
- C. Ellen van der Schoot,
- Jeroen den Dunnen,
- Manfred Wuhrer,
- Marc Ehlers,
- Gestur Vidarsson,
- Spinello Antinori,
- Cinzia Bassoli,
- Giovanna Bestetti,
- Mario Corbellino,
- Alice Covizzi,
- Angelica Lupo,
- Laura Milazzo,
- Marco Schiuma,
- Alessandro Torre,
- Brent Appelman,
- Diederik Beek van de,
- Marije K. Bomers,
- Justin Brabander de,
- Matthijs C. Brouwer,
- David T.P. Buis,
- Nora Chekrouni,
- Marit J. Gils van,
- Menno D. Jong de,
- Ayesha H.A. Lavell,
- Niels Mourik van,
- Sabine E. Olie,
- Edgar J.G. Peters,
- Tom D.Y. Reijnders,
- Michiel Schinkel,
- Alex R. Schuurman,
- Jonne J. Sikkens,
- Marleen A. Slim,
- Yvo M. Smulders,
- Alexander P.J. Vlaar,
- Lonneke A. Vught van,
- Joost W. Wiersinga
Affiliations
- Julie Van Coillie
- 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
- Tamas Pongracz
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands
- Johann Rahmöller
- 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
- Hung-Jen Chen
- Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam UMC, University of Amsterdam, the Netherlands
- Chiara Elisabeth Geyer
- Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam, the Netherlands
- Lonneke A. van Vught
- 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
- Jana Sophia Buhre
- Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany
- Tonći Šuštić
- 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
- Thijs Luc Junior van Osch
- 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
- Maurice Steenhuis
- 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
- Willianne Hoepel
- 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
- Wenjun Wang
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands
- Anne Sophie Lixenfeld
- Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany
- Jan Nouta
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands
- Sofie Keijzer
- 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
- Federica Linty
- 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
- Remco Visser
- 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
- Mads Delbo Larsen
- 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
- Emily Lara Martin
- Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany
- Inga Künsting
- Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany
- Selina Lehrian
- Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany
- Vera von Kopylow
- Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany
- Carsten Kern
- Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany
- Hanna Bele Lunding
- Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center of Schleswig-Holstein, Lübeck, Germany
- Menno de Winther
- Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam UMC, University of Amsterdam, the Netherlands
- Niels van Mourik
- 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
- Theo Rispens
- 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
- Tobias Graf
- Medical Department 2, University Heart Center of Schleswig-Holstein, Lübeck, Germany
- Marleen Adriana Slim
- 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
- René Peter Minnaar
- Amsterdam UMC Biobank, Amsterdam UMC, Amsterdam, the Netherlands
- Marije Kristianne Bomers
- Department of Internal Medicine, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands
- Jonne Jochum Sikkens
- Department of Internal Medicine, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands
- Alexander P.J. Vlaar
- Department of Intensive Care, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
- C. Ellen van der Schoot
- 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
- Jeroen den Dunnen
- Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam, the Netherlands
- Manfred Wuhrer
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands; Corresponding author.
- Marc Ehlers
- 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; Corresponding author.
- Gestur Vidarsson
- 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; Corresponding author.
- Spinello Antinori
- Cinzia Bassoli
- Giovanna Bestetti
- Mario Corbellino
- Alice Covizzi
- Angelica Lupo
- Laura Milazzo
- Marco Schiuma
- Alessandro Torre
- Brent Appelman
- Diederik Beek van de
- Marije K. Bomers
- Justin Brabander de
- Matthijs C. Brouwer
- David T.P. Buis
- Nora Chekrouni
- Marit J. Gils van
- Menno D. Jong de
- Ayesha H.A. Lavell
- Niels Mourik van
- Sabine E. Olie
- Edgar J.G. Peters
- Tom D.Y. Reijnders
- Michiel Schinkel
- Alex R. Schuurman
- Jonne J. Sikkens
- Marleen A. Slim
- Yvo M. Smulders
- Alexander P.J. Vlaar
- Lonneke A. Vught van
- Joost W. Wiersinga
- Journal volume & issue
-
Vol. 87
p. 104408
Abstract
Summary: 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: LSBR 1721, 1908; ZonMW 10430012010021, 09150161910033, 10430012010008; DFG 398859914, 400912066, 390884018; PMI; DOI4-Nr. 3; H2020-MSCA-ITN 721815.
