TY - JOUR
T1 - The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees
AU - Fatebenefratelli-Sacco Infectious Diseases Physicians group
AU - UMC COVID-19 S3/HCW study group
AU - Fatebenefratelli-Sacco Infectious Diseases Physicians group
AU - UMC COVID-19 S3/HCW study group
AU - Van Coillie, Julie
AU - Pongracz, Tamas
AU - Rahmöller, Johann
AU - Chen, Hung Jen
AU - Geyer, Chiara Elisabeth
AU - van Vught, Lonneke A.
AU - Buhre, Jana Sophia
AU - Šuštić, Tonći
AU - van Osch, Thijs Luc Junior
AU - Steenhuis, Maurice
AU - Hoepel, Willianne
AU - Wang, Wenjun
AU - Lixenfeld, Anne Sophie
AU - Nouta, Jan
AU - Keijzer, Sofie
AU - Linty, Federica
AU - Visser, Remco
AU - Larsen, Mads Delbo
AU - Martin, Emily Lara
AU - Künsting, Inga
AU - Lehrian, Selina
AU - von Kopylow, Vera
AU - Kern, Carsten
AU - Lunding, Hanna Bele
AU - de Winther, Menno
AU - van Mourik, Niels
AU - Rispens, Theo
AU - Graf, Tobias
AU - Slim, Marleen Adriana
AU - Minnaar, René Peter
AU - Bomers, Marije Kristianne
AU - Sikkens, Jonne Jochum
AU - Vlaar, Alexander P.J.
AU - van der Schoot, C. Ellen
AU - den Dunnen, Jeroen
AU - Wuhrer, Manfred
AU - Ehlers, Marc
AU - Vidarsson, Gestur
AU - Antinori, Spinello
AU - Bassoli, Cinzia
AU - Bestetti, Giovanna
AU - Corbellino, Mario
AU - Covizzi, Alice
AU - Lupo, Angelica
AU - Milazzo, Laura
AU - Schiuma, Marco
AU - Torre, Alessandro
AU - Appelman, Brent
AU - Beek van de, Diederik
AU - Brabander de, Justin
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85144022875&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2022.104408
DO - 10.1016/j.ebiom.2022.104408
M3 - Journal articles
C2 - 36529104
AN - SCOPUS:85144022875
SN - 2352-3964
VL - 87
SP - 104408
JO - EBioMedicine
JF - EBioMedicine
M1 - 104408
ER -
