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IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2
Humoral immunity to SARS-CoV-2 can be supplemented with polyclonal sera from convalescent donors or an engineered monoclonal antibody (mAb) product. While pentameric IgM antibodies are responsible for much of convalescent sera’s neutralizing capacity, all available mAbs are based on the monomeric Ig...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365875/ https://www.ncbi.nlm.nih.gov/pubmed/35938988 http://dx.doi.org/10.1084/jem.20220849 |
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author | Hale, Malika Netland, Jason Chen, Yu Thouvenel, Christopher D. Smith, Katherine Nabel Rich, Lucille M. Vanderwall, Elizabeth R. Miranda, Marcos C. Eggenberger, Julie Hao, Linhui Watson, Michael J. Mundorff, Charles C. Rodda, Lauren B. King, Neil P. Guttman, Miklos Gale, Michael Abraham, Jonathan Debley, Jason S. Pepper, Marion Rawlings, David J. |
author_facet | Hale, Malika Netland, Jason Chen, Yu Thouvenel, Christopher D. Smith, Katherine Nabel Rich, Lucille M. Vanderwall, Elizabeth R. Miranda, Marcos C. Eggenberger, Julie Hao, Linhui Watson, Michael J. Mundorff, Charles C. Rodda, Lauren B. King, Neil P. Guttman, Miklos Gale, Michael Abraham, Jonathan Debley, Jason S. Pepper, Marion Rawlings, David J. |
author_sort | Hale, Malika |
collection | PubMed |
description | Humoral immunity to SARS-CoV-2 can be supplemented with polyclonal sera from convalescent donors or an engineered monoclonal antibody (mAb) product. While pentameric IgM antibodies are responsible for much of convalescent sera’s neutralizing capacity, all available mAbs are based on the monomeric IgG antibody subtype. We now show that IgM mAbs derived from immune memory B cell receptors are potent neutralizers of SARS-CoV-2. IgM mAbs outperformed clonally identical IgG antibodies across a range of affinities and SARS-CoV-2 receptor-binding domain epitopes. Strikingly, efficacy against SARS-CoV-2 viral variants was retained for IgM but not for clonally identical IgG. To investigate the biological role for IgM memory in SARS-CoV-2, we also generated IgM mAbs from antigen-experienced IgM(+) memory B cells in convalescent donors, identifying a potent neutralizing antibody. Our results highlight the therapeutic potential of IgM mAbs and inform our understanding of the role for IgM memory against a rapidly mutating pathogen. |
format | Online Article Text |
id | pubmed-9365875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-93658752022-08-16 IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2 Hale, Malika Netland, Jason Chen, Yu Thouvenel, Christopher D. Smith, Katherine Nabel Rich, Lucille M. Vanderwall, Elizabeth R. Miranda, Marcos C. Eggenberger, Julie Hao, Linhui Watson, Michael J. Mundorff, Charles C. Rodda, Lauren B. King, Neil P. Guttman, Miklos Gale, Michael Abraham, Jonathan Debley, Jason S. Pepper, Marion Rawlings, David J. J Exp Med Brief Definitive Report Humoral immunity to SARS-CoV-2 can be supplemented with polyclonal sera from convalescent donors or an engineered monoclonal antibody (mAb) product. While pentameric IgM antibodies are responsible for much of convalescent sera’s neutralizing capacity, all available mAbs are based on the monomeric IgG antibody subtype. We now show that IgM mAbs derived from immune memory B cell receptors are potent neutralizers of SARS-CoV-2. IgM mAbs outperformed clonally identical IgG antibodies across a range of affinities and SARS-CoV-2 receptor-binding domain epitopes. Strikingly, efficacy against SARS-CoV-2 viral variants was retained for IgM but not for clonally identical IgG. To investigate the biological role for IgM memory in SARS-CoV-2, we also generated IgM mAbs from antigen-experienced IgM(+) memory B cells in convalescent donors, identifying a potent neutralizing antibody. Our results highlight the therapeutic potential of IgM mAbs and inform our understanding of the role for IgM memory against a rapidly mutating pathogen. Rockefeller University Press 2022-08-08 /pmc/articles/PMC9365875/ /pubmed/35938988 http://dx.doi.org/10.1084/jem.20220849 Text en © 2022 Hale et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Report Hale, Malika Netland, Jason Chen, Yu Thouvenel, Christopher D. Smith, Katherine Nabel Rich, Lucille M. Vanderwall, Elizabeth R. Miranda, Marcos C. Eggenberger, Julie Hao, Linhui Watson, Michael J. Mundorff, Charles C. Rodda, Lauren B. King, Neil P. Guttman, Miklos Gale, Michael Abraham, Jonathan Debley, Jason S. Pepper, Marion Rawlings, David J. IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2 |
title | IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2 |
title_full | IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2 |
title_fullStr | IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2 |
title_full_unstemmed | IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2 |
title_short | IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2 |
title_sort | igm antibodies derived from memory b cells are potent cross-variant neutralizers of sars-cov-2 |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365875/ https://www.ncbi.nlm.nih.gov/pubmed/35938988 http://dx.doi.org/10.1084/jem.20220849 |
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