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

Fatebenefratelli-Sacco Infectious Diseases Physicians group; UMC COVID-19 S3/HCW study group; Fatebenefratelli-Sacco Infectious Diseases Physicians group; UMC COVID-19 S3/HCW study group

doi:10.1016/j.ebiom.2022.104408

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

Fatebenefratelli-Sacco Infectious Diseases Physicians group, UMC COVID-19 S3/HCW study group, Fatebenefratelli-Sacco Infectious Diseases Physicians group, UMC COVID-19 S3/HCW study group

31 Citations (Scopus)

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: LSBR 1721, 1908; ZonMW 10430012010021, 09150161910033, 10430012010008; DFG 398859914, 400912066, 390884018; PMI; DOI4-Nr. 3; H2020-MSCA-ITN 721815.

Original language	English
Article number	104408
Journal	eBioMedicine
Volume	87
Pages (from-to)	104408
DOIs	https://doi.org/10.1016/j.ebiom.2022.104408
Publication status	Published - 01.01.2023

Funding

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: 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)

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

2.21-05 Immunology

Coronavirus related work

Research on SARS-CoV-2 / COVID-19

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ebiom.2022.104408

Cite this

Fatebenefratelli-Sacco Infectious Diseases Physicians group, UMC COVID-19 S3/HCW study group, Fatebenefratelli-Sacco Infectious Diseases Physicians group, & UMC COVID-19 S3/HCW study group (2023). The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees. eBioMedicine, 87, 104408. Article 104408. https://doi.org/10.1016/j.ebiom.2022.104408

@article{7ed73386d4154500b148700daf297ed8,

title = "The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees",

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: LSBR 1721, 1908; ZonMW 10430012010021, 09150161910033, 10430012010008; DFG 398859914, 400912066, 390884018; PMI; DOI4-Nr. 3; H2020-MSCA-ITN 721815.",

author = "\{Fatebenefratelli-Sacco Infectious Diseases Physicians group\} and \{UMC COVID-19 S3/HCW study group\} and \{Fatebenefratelli-Sacco Infectious Diseases Physicians group\} and \{UMC COVID-19 S3/HCW study group\} and \{Van Coillie\}, Julie and Tamas Pongracz and Johann Rahm{\"o}ller and Chen, \{Hung Jen\} and Geyer, \{Chiara Elisabeth\} and \{van Vught\}, \{Lonneke A.\} and Buhre, \{Jana Sophia\} and Ton{\'c}i {\v S}u{\v s}ti{\'c} and \{van Osch\}, \{Thijs Luc Junior\} and Maurice Steenhuis and Willianne Hoepel and Wenjun Wang and Lixenfeld, \{Anne Sophie\} and Jan Nouta and Sofie Keijzer and Federica Linty and Remco Visser and Larsen, \{Mads Delbo\} and Martin, \{Emily Lara\} and Inga K{\"u}nsting and Selina Lehrian and \{von Kopylow\}, Vera and Carsten Kern and Lunding, \{Hanna Bele\} and \{de Winther\}, Menno and \{van Mourik\}, Niels and Theo Rispens and Tobias Graf and Slim, \{Marleen Adriana\} and Minnaar, \{Ren{\'e} Peter\} and Bomers, \{Marije Kristianne\} and Sikkens, \{Jonne Jochum\} and Vlaar, \{Alexander P.J.\} and \{van der Schoot\}, \{C. Ellen\} and \{den Dunnen\}, Jeroen and Manfred Wuhrer and Marc Ehlers and Gestur Vidarsson and Spinello Antinori and Cinzia Bassoli and Giovanna Bestetti and Mario Corbellino and Alice Covizzi and Angelica Lupo and Laura Milazzo and Marco Schiuma and Alessandro Torre and Brent Appelman and \{Beek van de\}, Diederik and \{Brabander de\}, Justin",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2023",

month = jan,

day = "1",

doi = "10.1016/j.ebiom.2022.104408",

language = "English",

volume = "87",

pages = "104408",

journal = "eBioMedicine",

issn = "2352-3964",

publisher = "Elsevier B.V.",

}

Fatebenefratelli-Sacco Infectious Diseases Physicians group, UMC COVID-19 S3/HCW study group, Fatebenefratelli-Sacco Infectious Diseases Physicians group & UMC COVID-19 S3/HCW study group 2023, 'The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees', eBioMedicine, vol. 87, 104408, pp. 104408. https://doi.org/10.1016/j.ebiom.2022.104408

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees. / Fatebenefratelli-Sacco Infectious Diseases Physicians group; UMC COVID-19 S3/HCW study group; Fatebenefratelli-Sacco Infectious Diseases Physicians group et al.
In: eBioMedicine, Vol. 87, 104408, 01.01.2023, p. 104408.

Research output: Journal Articles › Journal articles › Research › peer-review

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

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 - https://www.scopus.com/pages/publications/85144022875

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 -

Fatebenefratelli-Sacco Infectious Diseases Physicians group, UMC COVID-19 S3/HCW study group, Fatebenefratelli-Sacco Infectious Diseases Physicians group, UMC COVID-19 S3/HCW study group. The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees. eBioMedicine. 2023 Jan 1;87:104408. 104408. doi: 10.1016/j.ebiom.2022.104408

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

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

Coronavirus related work

UN SDGs

Access to Document

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