Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines

in collaboration with the UMC COVID-19 S3/HCW study group; Fatebenefratelli-Sacco Infectious Diseases Physicians group; Radboud University Medical Center (RUMC) and COUGH1 study group

doi:10.1016/j.isci.2023.107619

Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines

in collaboration with the UMC COVID-19 S3/HCW study group, Fatebenefratelli-Sacco Infectious Diseases Physicians group, Radboud University Medical Center (RUMC) and COUGH1 study group

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

IgG antibodies are important mediators of vaccine-induced immunity through complement- and Fc receptor-dependent effector functions. Both are influenced by the composition of the conserved N-linked glycan located in the IgG Fc domain. Here, we compared the anti-Spike (S) IgG1 Fc glycosylation profiles in response to mRNA, adenoviral, and protein-based COVID-19 vaccines by mass spectrometry (MS). All vaccines induced a transient increase of antigen-specific IgG1 Fc galactosylation and sialylation. An initial, transient increase of afucosylated IgG was induced by membrane-encoding S protein formulations. A fucose-sensitive ELISA for antigen-specific IgG (FEASI) exploiting FcγRIIIa affinity for afucosylated IgG was used as an orthogonal method to confirm the LC-MS-based afucosylation readout. Our data suggest that vaccine-induced anti-S IgG glycosylation is dynamic, and although variation is seen between different vaccine platforms and individuals, the evolution of glycosylation patterns display marked overlaps.

Original language	English
Article number	107619
Journal	iScience
Volume	26
Issue number	9
DOIs	https://doi.org/10.1016/j.isci.2023.107619
Publication status	Published - 15 Sept 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Funding

We thank the Academic Medical Centre of the University of Amsterdam, the Sanquin Blood Supply Foundation, Janssen Vaccines and Prevention B.V. and Radboud University Medical Center (RUMC) & Bavarian Nordic A/S. We furthermore thank all cohort participants, to whom we are greatly indebted for their extensive participation. Funding: Landsteiner foundation for Blood Transfusion Research (LSBR) grants 1721 and 1908 (G.V.). ZonMW COVID-19 grant 1043001 201 0021 (G.V.). Netherlands Organization 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 (L.A.V.V.). Advancing knowledge for the clinical and public health response to the 2019-nCoV epidemic [H2020-SC1-PHE-CORONAVIRUS-2020 grant agreement ID: 101003608 ] (M.W.). Semper Ardens Carlsberg Foundation (M.W.). This project has been funded in whole or in part with federal funds from the Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, under Other Transaction Agreement HHSO100201700018C. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the United States Department of Health and Human Services or its components. Conceptualization: G.V. M.W. C.E.v.d.S. A.V. and D.E.S. Methodology: G.V. M.W. J.V.C. T.P. and T.S. Formal analysis: J.V.C. T.P. T.S. and S.K. Investigation: J.V.C. T.S. T.P. S.K. M.S. F.L. R.V. W.W. and J.N. Resources: D.S. L.A.v.V. W.H. M.A.S. R.M. M.K.B. J.J.S. A.S. D.S. M.A.N. B.G.M. R.R. M.L.G. and the UMC COVID-19 S3/HCW study group, Fatebenefratelli-Sacco Infectious Diseases Physicians group and Radboud University Medical Center (RUMC) & Bavarian Nordic (BN) A/S. Data curation: J.V.C. T.S. T.P. S.K. and M.S. Writing – Original draft: G.V. M.W. J.V.C. T.P. and R.R. Writing – Review and editing: J.V.C. T.P. T.S. W.W. J.N. M.L.G. S.K. F.L. O.C. J.B.D.K. R.V. L.A.v.V. M.A.S. N.v.M. M.J.S. A.S. D.E.S. M.S. T.R. M.A.N. B.G.N. A.P.J.V. C.E.v.d.S. R.R. M.W. and G.V. Visualization: T.P. and J.V.C. Supervision: G.V. M.W. A.V. and R.R. Project administration: G.V. M.W. and M.S. Funding acquisition: G.V. M.W. T.P. and Radboud University Medical Center (RUMC) & COUGH1. M.L.G. and R.R. are employees of Janssen Pharmaceuticals and M.L.G. is a shareholder in Johnson & Johnson. A.S. and W.A.d.J. are employees at AdaptVac, a company commercializing virus-like particle display technology and vaccines, including several patents. A.S. A.S. T.G.T. and M.N. are founders of AdaptVac and listed as coinventors on a patent covering the AP205 CLP vaccine platform technology (WO2016112921 A1) licensed to AdaptVac. Janssen Pharmaceuticals sponsored IgG glycosylation analysis at LUMC. Sanquin provided consultancy services to Janssen Pharmaceuticals during this study. All other authors declare they have no conflicts of interests. Funding: Landsteiner foundation for Blood Transfusion Research (LSBR) grants 1721 and 1908 (G.V.). ZonMW COVID-19 grant 1043001 201 0021 (G.V.). Netherlands Organization 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 (L.A.V.V.). Advancing knowledge for the clinical and public health response to the 2019-nCoV epidemic [H2020-SC1-PHE-CORONAVIRUS-2020 grant agreement ID: 101003608 ] (M.W.). Semper Ardens Carlsberg Foundation (M.W.). This project has been funded in whole or in part with federal funds from the Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, under Other Transaction Agreement HHSO100201700018C. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the United States Department of Health and Human Services or its components.

Funders	Funder number
Bavarian Nordic A/S
Fatebenefratelli-Sacco Infectious Diseases Physicians group and Radboud University Medical Center
H2020-SC1-PHE-CORONAVIRUS-2020	101003608
Janssen Vaccines and Prevention B.V. and Radboud University Medical Center
Semper Ardens Carlsberg Foundation
U.S. Department of Health and Human Services
Janssen Pharmaceuticals	WO2016112921 A1
Landsteiner Foundation for Blood Transfusion Research	1721, 1908, 09150161910033
Biomedical Advanced Research and Development Authority	HHSO100201700018C
Administration for Strategic Preparedness and Response
ZonMw
NIZW/ Universiteit van Amsterdam
Radboud Universitair Medisch Centrum
Stichting Sanquin Bloedvoorziening

Keywords

Glycomics
Immune response
Immunology
Microbiology

UN SDGs

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

Access to Document

10.1016/j.isci.2023.107619Licence: CC BY-NC-ND

PIIS2589004223016966Final published version, 4.29 MBLicence: CC BY-NC-ND

Cite this

in collaboration with the UMC COVID-19 S3/HCW study group, Fatebenefratelli-Sacco Infectious Diseases Physicians group, & Radboud University Medical Center (RUMC) and COUGH1 study group (2023). Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines. iScience, 26(9), Article 107619. https://doi.org/10.1016/j.isci.2023.107619

@article{530ec5273cc247d693bee21e4db32ac5,

title = "Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines",

abstract = "IgG antibodies are important mediators of vaccine-induced immunity through complement- and Fc receptor-dependent effector functions. Both are influenced by the composition of the conserved N-linked glycan located in the IgG Fc domain. Here, we compared the anti-Spike (S) IgG1 Fc glycosylation profiles in response to mRNA, adenoviral, and protein-based COVID-19 vaccines by mass spectrometry (MS). All vaccines induced a transient increase of antigen-specific IgG1 Fc galactosylation and sialylation. An initial, transient increase of afucosylated IgG was induced by membrane-encoding S protein formulations. A fucose-sensitive ELISA for antigen-specific IgG (FEASI) exploiting FcγRIIIa affinity for afucosylated IgG was used as an orthogonal method to confirm the LC-MS-based afucosylation readout. Our data suggest that vaccine-induced anti-S IgG glycosylation is dynamic, and although variation is seen between different vaccine platforms and individuals, the evolution of glycosylation patterns display marked overlaps.",

keywords = "Glycomics, Immune response, Immunology, Microbiology",

author = "{in collaboration with the UMC COVID-19 S3/HCW study group} and {Fatebenefratelli-Sacco Infectious Diseases Physicians group} and {Radboud University Medical Center (RUMC) and COUGH1 study group} and {Van Coillie}, Julie and Tamas Pongracz and Ton{\'c}i {\v S}u{\v s}ti{\'c} and Wenjun Wang and Jan Nouta and {Le Gars}, Mathieu and Sofie Keijzer and Federica Linty and Olvi Cristianawati and Keijser, {Jim B.D.} and Remco Visser and {van Vught}, {Lonneke A.} and Slim, {Marleen A.} and {van Mourik}, Niels and Smit, {Merel J.} and Adam Sander and Schmidt, {David E.} and Maurice Steenhuis and Theo Rispens and Nielsen, {Morten A.} and Mordm{\"u}ller, {Benjamin G.} and Vlaar, {Alexander P.J.} and {Ellen van der Schoot}, C. and Ramon Roozendaal and Manfred Wuhrer and Gestur Vidarsson and Brent Appelman and {van de Beek}, Diederik and Bomers, {Marije K.} and {de Brabander}, Justin and Brouwer, {Matthijs C.} and Buis, {David T.P.} and Nora Chekrouni and {van Gils}, {Marit J.} and {de Jong}, {Menno D.} and Lavell, {Ayesha H.A.} and Olie, {Sabine E.} and Peters, {Edgar J.G.} and Reijnders, {Tom D.Y.} and Michiel Schinkel and Schuurman, {Alex R.} and Sikkens, {Jonne J.} and Smulders, {Yvo M.} and Wiersinga, {Joost W.} and Antinori Spinello and Cinzia Bassoli and Giovanna Bestetti and Mario Corbellino and Alice Covizzi and Angelica Lupo",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = sep,

day = "15",

doi = "10.1016/j.isci.2023.107619",

language = "English",

volume = "26",

journal = "iScience",

issn = "2589-0042",

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number = "9",

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in collaboration with the UMC COVID-19 S3/HCW study group, Fatebenefratelli-Sacco Infectious Diseases Physicians group & Radboud University Medical Center (RUMC) and COUGH1 study group 2023, 'Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines', iScience, vol. 26, no. 9, 107619. https://doi.org/10.1016/j.isci.2023.107619

Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines. / in collaboration with the UMC COVID-19 S3/HCW study group; Fatebenefratelli-Sacco Infectious Diseases Physicians group; Radboud University Medical Center (RUMC) and COUGH1 study group.
In: iScience, Vol. 26, No. 9, 107619, 15.09.2023.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines

AU - in collaboration with the UMC COVID-19 S3/HCW study group

AU - Fatebenefratelli-Sacco Infectious Diseases Physicians group

AU - Radboud University Medical Center (RUMC) and COUGH1 study group

AU - Van Coillie, Julie

AU - Pongracz, Tamas

AU - Šuštić, Tonći

AU - Wang, Wenjun

AU - Nouta, Jan

AU - Le Gars, Mathieu

AU - Keijzer, Sofie

AU - Linty, Federica

AU - Cristianawati, Olvi

AU - Keijser, Jim B.D.

AU - Visser, Remco

AU - van Vught, Lonneke A.

AU - Slim, Marleen A.

AU - van Mourik, Niels

AU - Smit, Merel J.

AU - Sander, Adam

AU - Schmidt, David E.

AU - Steenhuis, Maurice

AU - Rispens, Theo

AU - Nielsen, Morten A.

AU - Mordmüller, Benjamin G.

AU - Vlaar, Alexander P.J.

AU - Ellen van der Schoot, C.

AU - Roozendaal, Ramon

AU - Wuhrer, Manfred

AU - Vidarsson, Gestur

AU - Appelman, Brent

AU - van de Beek, Diederik

AU - Bomers, Marije K.

AU - de Brabander, Justin

AU - Brouwer, Matthijs C.

AU - Buis, David T.P.

AU - Chekrouni, Nora

AU - van Gils, Marit J.

AU - de Jong, Menno D.

AU - Lavell, Ayesha H.A.

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 - Smulders, Yvo M.

AU - Wiersinga, Joost W.

AU - Spinello, Antinori

AU - Bassoli, Cinzia

AU - Bestetti, Giovanna

AU - Corbellino, Mario

AU - Covizzi, Alice

AU - Lupo, Angelica

PY - 2023/9/15

Y1 - 2023/9/15

N2 - IgG antibodies are important mediators of vaccine-induced immunity through complement- and Fc receptor-dependent effector functions. Both are influenced by the composition of the conserved N-linked glycan located in the IgG Fc domain. Here, we compared the anti-Spike (S) IgG1 Fc glycosylation profiles in response to mRNA, adenoviral, and protein-based COVID-19 vaccines by mass spectrometry (MS). All vaccines induced a transient increase of antigen-specific IgG1 Fc galactosylation and sialylation. An initial, transient increase of afucosylated IgG was induced by membrane-encoding S protein formulations. A fucose-sensitive ELISA for antigen-specific IgG (FEASI) exploiting FcγRIIIa affinity for afucosylated IgG was used as an orthogonal method to confirm the LC-MS-based afucosylation readout. Our data suggest that vaccine-induced anti-S IgG glycosylation is dynamic, and although variation is seen between different vaccine platforms and individuals, the evolution of glycosylation patterns display marked overlaps.

AB - IgG antibodies are important mediators of vaccine-induced immunity through complement- and Fc receptor-dependent effector functions. Both are influenced by the composition of the conserved N-linked glycan located in the IgG Fc domain. Here, we compared the anti-Spike (S) IgG1 Fc glycosylation profiles in response to mRNA, adenoviral, and protein-based COVID-19 vaccines by mass spectrometry (MS). All vaccines induced a transient increase of antigen-specific IgG1 Fc galactosylation and sialylation. An initial, transient increase of afucosylated IgG was induced by membrane-encoding S protein formulations. A fucose-sensitive ELISA for antigen-specific IgG (FEASI) exploiting FcγRIIIa affinity for afucosylated IgG was used as an orthogonal method to confirm the LC-MS-based afucosylation readout. Our data suggest that vaccine-induced anti-S IgG glycosylation is dynamic, and although variation is seen between different vaccine platforms and individuals, the evolution of glycosylation patterns display marked overlaps.

KW - Glycomics

KW - Immune response

KW - Immunology

KW - Microbiology

UR - http://www.scopus.com/inward/record.url?scp=85169841393&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2023.107619

DO - 10.1016/j.isci.2023.107619

M3 - Article

AN - SCOPUS:85169841393

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 9

M1 - 107619

ER -

in collaboration with the UMC COVID-19 S3/HCW study group, Fatebenefratelli-Sacco Infectious Diseases Physicians group, Radboud University Medical Center (RUMC) and COUGH1 study group. Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines. iScience. 2023 Sept 15;26(9):107619. doi: 10.1016/j.isci.2023.107619

Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

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Cite this