Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines
Julie Van Coillie, Tamás Pongrácz, Tonći Šuštić, Wenjun Wang, Jan Nouta, Mathieu Le Gars, Sofie Keijzer, Federica Linty, Olvi Cristianawati, Jim Keijser, Remco Visser, Lonneke A. van Vught, Marleen A. Slim, Niels van Mourik, Merel Smit, Adam F. Sander, David E. Schmidt, Maurice Steenhuis, Theo Rispens, Morten A. Nielsen, Benjamin Mordmüller, Alexander P. J. Vlaar, C. Ellen van der Schoot, Ramon Roozendaal, Manfred Wuhrer, Gestur Vidarsson, Brent Appelman, Diederik van de Beek, Marije K. Bomers, Justin de Brabander, Matthijs C. Brouwer, David T.P. Buis, Nora Chekrouni, Marit J. van Gils, Menno D. de Jong, A. H. Ayesha Lavell, Niels van Mourik, 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. van Vught, Joost W. Wiersinga, Antinori Spinello, Cinzia Bassoli, Giovanna Bestetti, Mario Corbellino, Alice Covizzi, A. Lupo, Laura Milazzo, Marco Schiuma, Alessandro Torre, Willem A. de Jongh, Ali Salanti, Thor G. Theander, Matthew B. B. McCall, Meral Esen
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.