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.
- Van Coillie, J.
- Pongracz, T.
- Rahmöller, J.
- Chen, H. J.
- Geyer, C. E.
- van Vught, L. A.
- Buhre, J. S.
- Šuštić, T.
- van Osch, T. L. J.
- Steenhuis, M.
- Hoepel, W.
- Wang, W.
- Lixenfeld, A. S.
- Nouta, J.
- Keijzer, S.
- Linty, F.
- Visser, R.
- Larsen, M. D.
- Martin, E. L.
- Künsting, I.
- Lehrian, S.
- von Kopylow, V.
- Kern, C.
- Lunding, H. B.
- de Winther, M.
- van Mourik, N.
- Rispens, T.
- Graf, T.
- Slim, M. A.
- Minnaar, R. P.
- Bomers, M. K.
- Sikkens, J. J.
- Vlaar, A. P. J.
- van der Schoot, C. E.
- den Dunnen, J.
- Wuhrer, M.
- Ehlers, M.
- Vidarsson, G.
Keywords
- Antibodies
- Covid-19
- Fucosylation
- Glycosylation
- mRNA Vaccine
