Generic Portal

TY - JOUR

T1 - The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees

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 - Fatebenefratelli-Sacco Infectious Diseases Physicians group

AU - Bomers, Marije Kristianne

AU - Sikkens, Jonne Jochum

AU - Vlaar, Alexander P. J.

AU - van der Schoot, C. Ellen

AU - UMC COVID-19 S3/HCW study group

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 - Bomers, Marije K.

AU - Brabander de, Justin

AU - Brouwer, Matthijs C.

AU - Buis, David T. P.

AU - Chekrouni, Nora

AU - Gils van, Marit J.

AU - Jong de, Menno D.

AU - Lavell, Ayesha H. A.

AU - Mourik van, Niels

AU - Olie, Sabine E.

AU - Peters, Edgar J. G.

AU - Reijnders, Tom D. Y.

AU - Schinkel, Michiel

AU - Schuurman, Alex R.

AU - Sikkens, Jonne J.

AU - Slim, Marleen A.

AU - Smulders, Yvo M.

AU - Vught van, Lonneke A.

AU - Wiersinga, Joost W.

N1 - Funding Information: LSBR 1721, 1908; ZonMW 10430012010021, 09150161910033, 10430012010008; DFG 398859914, 400912066, 390884018; PMI; DOI4-Nr. 3; H2020-MSCA-ITN 721815.We thank the Academic Medical Centre of the University of Amsterdam, the Sanquin Blood Supply Foundation and The Fatebenefratelli-Sacco Infectious Diseases Physicians Group. We are greatly indebted to all cohort participants for their extensive participation. Funding: Landsteiner Foundation for Blood Transfusion Research (LSBR) grants 1721 and 1908 (GV) ZonMw COVID-19 grants 1043001 201 0021 (GV). Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) 398859914 (EH 221/10-1); 400912066 (EH 221/11-1); and 390884018 (Germany's Excellence Strategies - EXC 2167, Precision Medicine in Chronic Inflammation (PMI)) (ME). Federal State Schleswig-Holstein, Germany (COVID-19 Research Initiative Schleswig-Holstein; DOI4-Nr. 3) (ME). European Union's Horizon 2020 research and innovation program H2020-MSCA-ITN grant agreement number 721815 (MW/TP). Netherlands Organisation for Health Research and Development ZonMw & the Amsterdam UMC Corona Research Fund (Amsterdam UMC COVID-19 S3/HCW study group). The Netherlands Organisation for Health Research and Development ZonMW VENI grant, Grant number 09150161910033 (LAVV). ZonMW COVID-19 grant 10430012010008 (JDD) Funding Information: Funding: Landsteiner Foundation for Blood Transfusion Research (LSBR) grants 1721 and 1908 (GV) ZonMw COVID-19 grants 1043001 201 0021 (GV). Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) 398859914 (EH 221/10-1); 400912066 (EH 221/11-1); and 390884018 (Germany's Excellence Strategies - EXC 2167, Precision Medicine in Chronic Inflammation (PMI)) (ME). Federal State Schleswig-Holstein, Germany (COVID-19 Research Initiative Schleswig-Holstein; DOI4-Nr. 3) (ME). European Union's Horizon 2020 research and innovation program H2020-MSCA-ITN grant agreement number 721815 (MW/TP). Netherlands Organisation for Health Research and Development ZonMw & the Amsterdam UMC Corona Research Fund (Amsterdam UMC COVID-19 S3/HCW study group). The Netherlands Organisation for Health Research and Development ZonMW VENI grant, Grant number 09150161910033 (LAVV). ZonMW COVID-19 grant 10430012010008 (JDD) 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.

KW - Antibodies

KW - COVID-19

KW - Fucosylation

KW - Glycosylation

KW - mRNA Vaccine

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 - Article

C2 - 36529104

VL - 87

SP - 104408

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

M1 - 104408

ER -