Discriminating cross-reactivity in polyclonal IgG1 responses against SARS-CoV-2 variants of concern

Danique M H van Rijswijck; Albert Bondt; Max Hoek; Karlijn van der Straten; Tom G Caniels; Meliawati Poniman; Dirk Eggink; Chantal Reusken; Godelieve J de Bree; Rogier W Sanders; Marit J van Gils; Albert J R Heck

doi:10.1038/s41467-022-33899-1

Discriminating cross-reactivity in polyclonal IgG1 responses against SARS-CoV-2 variants of concern

Danique M H van Rijswijck
, Albert Bondt
, Max Hoek
, Karlijn van der Straten
, Tom G Caniels
, Meliawati Poniman
, Dirk Eggink
, Chantal Reusken
, Godelieve J de Bree
, Rogier W Sanders
, Marit J van Gils
, Albert J R Heck^*

^*Corresponding author for this work

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

Abstract

Existing assays to measure antibody cross-reactivity against different SARS-CoV-2 spike (S) protein variants lack the discriminatory power to provide insights at the level of individual clones. Using a mass spectrometry-based approach we are able to monitor individual donors' IgG1 clonal responses following a SARS-CoV-2 infection. We monitor the plasma clonal IgG1 profiles of 8 donors who had experienced an infection by either the wild type Wuhan Hu-1 virus or one of 3 VOCs (Alpha, Beta and Gamma). In these donors we chart the full plasma IgG1 repertoires as well as the IgG1 repertoires targeting the SARS-CoV-2 spike protein trimer VOC antigens. The plasma of each donor contains numerous anti-spike IgG1 antibodies, accounting for <0.1% up to almost 10% of all IgG1s. Some of these antibodies are VOC-specific whereas others do recognize multiple or even all VOCs. We show that in these polyclonal responses, each clone exhibits a distinct cross-reactivity and also distinct virus neutralization capacity. These observations support the need for a more personalized look at the antibody clonal responses to infectious diseases.

Original language	English
Article number	6103
Number of pages	10
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-33899-1
Publication status	Published - 15 Oct 2022

Bibliographical note

Funding Information:
This research received funding through the Dutch Research Council (NWO) funding the Netherlands Proteomics Centre through the X-omics Road Map program (project 184.034.019) and Gravitation Subgrant 00022 from the Institute for Chemical Immunology (D.M.H.v.R. and A.B.). A.J.R.H. acknowledges support from the Netherlands Organization for Scientific Research (NWO) through the Spinoza Award SPI.2017.028 to A.J.R.H., R.W.S. acknowledges support from the Netherlands Organization for Scientific Research (NWO) through a Vici grant 91818627. The authors also acknowledge support from the Bill & Melinda Gates Foundation through grant INV-024617 (M.J.v.G.). M.J.v.G. is a recipient of an Amsterdam UMC AMC Fellowship.

Publisher Copyright:
© 2022, The Author(s).

Keywords

Antibodies, Neutralizing
Antibodies, Viral
Antigens, Viral
COVID-19
Humans
Immunoglobulin G
SARS-CoV-2
Spike Glycoprotein, Coronavirus

UN SDGs

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

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s41467-022-33899-1Final published version, 1.41 MBLicence: CC BY

Cite this

van Rijswijck, D. M. H., Bondt, A., Hoek, M., van der Straten, K., Caniels, T. G., Poniman, M., Eggink, D., Reusken, C., de Bree, G. J., Sanders, R. W., van Gils, M. J., & Heck, A. J. R. (2022). Discriminating cross-reactivity in polyclonal IgG1 responses against SARS-CoV-2 variants of concern. Nature Communications, 13(1), Article 6103. https://doi.org/10.1038/s41467-022-33899-1

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abstract = "Existing assays to measure antibody cross-reactivity against different SARS-CoV-2 spike (S) protein variants lack the discriminatory power to provide insights at the level of individual clones. Using a mass spectrometry-based approach we are able to monitor individual donors' IgG1 clonal responses following a SARS-CoV-2 infection. We monitor the plasma clonal IgG1 profiles of 8 donors who had experienced an infection by either the wild type Wuhan Hu-1 virus or one of 3 VOCs (Alpha, Beta and Gamma). In these donors we chart the full plasma IgG1 repertoires as well as the IgG1 repertoires targeting the SARS-CoV-2 spike protein trimer VOC antigens. The plasma of each donor contains numerous anti-spike IgG1 antibodies, accounting for <0.1\% up to almost 10\% of all IgG1s. Some of these antibodies are VOC-specific whereas others do recognize multiple or even all VOCs. We show that in these polyclonal responses, each clone exhibits a distinct cross-reactivity and also distinct virus neutralization capacity. These observations support the need for a more personalized look at the antibody clonal responses to infectious diseases.",

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note = "Funding Information: This research received funding through the Dutch Research Council (NWO) funding the Netherlands Proteomics Centre through the X-omics Road Map program (project 184.034.019) and Gravitation Subgrant 00022 from the Institute for Chemical Immunology (D.M.H.v.R. and A.B.). A.J.R.H. acknowledges support from the Netherlands Organization for Scientific Research (NWO) through the Spinoza Award SPI.2017.028 to A.J.R.H., R.W.S. acknowledges support from the Netherlands Organization for Scientific Research (NWO) through a Vici grant 91818627. The authors also acknowledge support from the Bill \& Melinda Gates Foundation through grant INV-024617 (M.J.v.G.). M.J.v.G. is a recipient of an Amsterdam UMC AMC Fellowship. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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AU - de Bree, Godelieve J

AU - Sanders, Rogier W

AU - van Gils, Marit J

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Discriminating cross-reactivity in polyclonal IgG1 responses against SARS-CoV-2 variants of concern

Abstract

Bibliographical note

Keywords

UN SDGs

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