The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees
Julie Van Coillie, Tamás Pongrácz, Johann Rahmöller, Hung‐Jen Chen, Chiara E. Geyer, Lonneke A. van Vught, Jana Sophia Buhre, Tonći Šuštić, Thijs L. J. van Osch, Maurice Steenhuis, Willianne Hoepel, Wenjun Wang, Anne S. Lixenfeld, Jan Nouta, Sofie Keijzer, Federica Linty, Remco Visser, Mads Delbo Larsen, Emily Martin, Inga Künsting, Selina Lehrian, Vera von Kopylow, Carsten Kern, Hanna B. Lunding, Menno P.J. de Winther, Niels van Mourik, Theo Rispens, Tobias Graf, Marleen A. Slim, René Minnaar, Marije K. Bomers, Jonne J. 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, A. Lupo, Laura Milazzo, Marco Schiuma, Alessandro Torre, 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, M.C.M. 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
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.