Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines

Julie Van Coillie; Tamas Pongracz; Tonći Šuštić; Wenjun Wang; Jan Nouta; Mathieu Le Gars; Sofie Keijzer; Federica Linty; Olvi Cristianawati; Jim B D Keijser; Remco Visser; Lonneke A van Vught; Marleen A Slim; Niels van Mourik; Merel J Smit; Adam Sander; David E Schmidt; Maurice Steenhuis; Theo Rispens; Morten A Nielsen; Benjamin G Mordmüller; Alexander P J Vlaar; C Ellen van der Schoot; Ramon Roozendaal; Manfred Wuhrer; Gestur Vidarsson; UMC COVID-19 S3/HCW study group; Fatebenefratelli-Sacco Infectious Diseases Physicians group; Radboud University Medical Center (RUMC) and COUGH1 study group

doi:10.1016/j.isci.2023.107619

Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines

iScience. 2023 Aug 14;26(9):107619. doi: 10.1016/j.isci.2023.107619. eCollection 2023 Sep 15.

Authors

Julie Van Coillie^{1

2}, Tamas Pongracz³, Tonći Šuštić^{1

2}, Wenjun Wang³, Jan Nouta³, Mathieu Le Gars⁴, Sofie Keijzer⁵, Federica Linty^{1

2}, Olvi Cristianawati⁵, Jim B D Keijser⁵, Remco Visser^{1

2}, Lonneke A van Vught^{6

7}, Marleen A Slim^{6

7}, Niels van Mourik^{6

7}, Merel J Smit⁸, Adam Sander^{9

10}, David E Schmidt¹, Maurice Steenhuis⁵, Theo Rispens⁵, Morten A Nielsen⁹, Benjamin G Mordmüller⁸, Alexander P J Vlaar^{7

11}, C Ellen van der Schoot¹, Ramon Roozendaal⁴, Manfred Wuhrer³, Gestur Vidarsson^{1

2}; UMC COVID-19 S3/HCW study group; Fatebenefratelli-Sacco Infectious Diseases Physicians group; Radboud University Medical Center (RUMC) and COUGH1 study group

Collaborators

Affiliations

¹ Department of Experimental Immunohematology, Sanquin Research, Amsterdam, the Netherlands.
² Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, the Netherlands.
³ Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands.
⁴ Janssen Vaccines & Prevention B.V., Leiden, the Netherlands.
⁵ Department of Immunopathology, Sanquin Research, Amsterdam, the Netherlands.
⁶ Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam, the Netherlands.
⁷ Department of Intensive Care, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
⁸ Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
⁹ Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹⁰ AdaptVac Aps, Copenhagen, Denmark.
¹¹ Laboratory of Experimental Intensive Care and Anaesthesiology, L.E.I.C.A., Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Abstract

IgG antibodies are important mediators of vaccine-induced immunity through complement- and Fc receptor-dependent effector functions. Both are influenced by the composition of the conserved N-linked glycan located in the IgG Fc domain. Here, we compared the anti-Spike (S) IgG1 Fc glycosylation profiles in response to mRNA, adenoviral, and protein-based COVID-19 vaccines by mass spectrometry (MS). All vaccines induced a transient increase of antigen-specific IgG1 Fc galactosylation and sialylation. An initial, transient increase of afucosylated IgG was induced by membrane-encoding S protein formulations. A fucose-sensitive ELISA for antigen-specific IgG (FEASI) exploiting FcγRIIIa affinity for afucosylated IgG was used as an orthogonal method to confirm the LC-MS-based afucosylation readout. Our data suggest that vaccine-induced anti-S IgG glycosylation is dynamic, and although variation is seen between different vaccine platforms and individuals, the evolution of glycosylation patterns display marked overlaps.

Keywords: Glycomics; Immune response; Immunology; Microbiology.