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IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding
The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2 or IgG3. We found that many influenza vi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536032/ https://www.ncbi.nlm.nih.gov/pubmed/36203556 http://dx.doi.org/10.1101/2022.09.27.509738 |
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author | Bolton, Marcus J. Arevalo, Claudia P. Griesman, Trevor Li, Shuk Hang Bates, Paul Wilson, Patrick C. Hensley, Scott E. |
author_facet | Bolton, Marcus J. Arevalo, Claudia P. Griesman, Trevor Li, Shuk Hang Bates, Paul Wilson, Patrick C. Hensley, Scott E. |
author_sort | Bolton, Marcus J. |
collection | PubMed |
description | The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2 or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded, and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 strain of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for finetuning effector functionality, but also for binding and neutralization of antigenically drifted viruses. |
format | Online Article Text |
id | pubmed-9536032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-95360322022-10-07 IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding Bolton, Marcus J. Arevalo, Claudia P. Griesman, Trevor Li, Shuk Hang Bates, Paul Wilson, Patrick C. Hensley, Scott E. bioRxiv Article The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2 or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded, and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 strain of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for finetuning effector functionality, but also for binding and neutralization of antigenically drifted viruses. Cold Spring Harbor Laboratory 2022-09-28 /pmc/articles/PMC9536032/ /pubmed/36203556 http://dx.doi.org/10.1101/2022.09.27.509738 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Bolton, Marcus J. Arevalo, Claudia P. Griesman, Trevor Li, Shuk Hang Bates, Paul Wilson, Patrick C. Hensley, Scott E. IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding |
title | IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding |
title_full | IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding |
title_fullStr | IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding |
title_full_unstemmed | IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding |
title_short | IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding |
title_sort | igg3 subclass antibodies recognize antigenically drifted influenza viruses and sars-cov-2 variants through efficient bivalent binding |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536032/ https://www.ncbi.nlm.nih.gov/pubmed/36203556 http://dx.doi.org/10.1101/2022.09.27.509738 |
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