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Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection

Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately...

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Autores principales: Khatamzas, Elham, Antwerpen, Markus H., Rehn, Alexandra, Graf, Alexander, Hellmuth, Johannes Christian, Hollaus, Alexandra, Mohr, Anne-Wiebe, Gaitzsch, Erik, Weiglein, Tobias, Georgi, Enrico, Scherer, Clemens, Stecher, Stephanie-Susanne, Gruetzner, Stefanie, Blum, Helmut, Krebs, Stefan, Reischer, Anna, Leutbecher, Alexandra, Subklewe, Marion, Dick, Andrea, Zange, Sabine, Girl, Philipp, Müller, Katharina, Weigert, Oliver, Hopfner, Karl-Peter, Stemmler, Hans-Joachim, von Bergwelt-Baildon, Michael, Keppler, Oliver T., Wölfel, Roman, Muenchhoff, Maximilian, Moosmann, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508331/
https://www.ncbi.nlm.nih.gov/pubmed/36151076
http://dx.doi.org/10.1038/s41467-022-32772-5
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author Khatamzas, Elham
Antwerpen, Markus H.
Rehn, Alexandra
Graf, Alexander
Hellmuth, Johannes Christian
Hollaus, Alexandra
Mohr, Anne-Wiebe
Gaitzsch, Erik
Weiglein, Tobias
Georgi, Enrico
Scherer, Clemens
Stecher, Stephanie-Susanne
Gruetzner, Stefanie
Blum, Helmut
Krebs, Stefan
Reischer, Anna
Leutbecher, Alexandra
Subklewe, Marion
Dick, Andrea
Zange, Sabine
Girl, Philipp
Müller, Katharina
Weigert, Oliver
Hopfner, Karl-Peter
Stemmler, Hans-Joachim
von Bergwelt-Baildon, Michael
Keppler, Oliver T.
Wölfel, Roman
Muenchhoff, Maximilian
Moosmann, Andreas
author_facet Khatamzas, Elham
Antwerpen, Markus H.
Rehn, Alexandra
Graf, Alexander
Hellmuth, Johannes Christian
Hollaus, Alexandra
Mohr, Anne-Wiebe
Gaitzsch, Erik
Weiglein, Tobias
Georgi, Enrico
Scherer, Clemens
Stecher, Stephanie-Susanne
Gruetzner, Stefanie
Blum, Helmut
Krebs, Stefan
Reischer, Anna
Leutbecher, Alexandra
Subklewe, Marion
Dick, Andrea
Zange, Sabine
Girl, Philipp
Müller, Katharina
Weigert, Oliver
Hopfner, Karl-Peter
Stemmler, Hans-Joachim
von Bergwelt-Baildon, Michael
Keppler, Oliver T.
Wölfel, Roman
Muenchhoff, Maximilian
Moosmann, Andreas
author_sort Khatamzas, Elham
collection PubMed
description Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design.
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spelling pubmed-95083312022-09-25 Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection Khatamzas, Elham Antwerpen, Markus H. Rehn, Alexandra Graf, Alexander Hellmuth, Johannes Christian Hollaus, Alexandra Mohr, Anne-Wiebe Gaitzsch, Erik Weiglein, Tobias Georgi, Enrico Scherer, Clemens Stecher, Stephanie-Susanne Gruetzner, Stefanie Blum, Helmut Krebs, Stefan Reischer, Anna Leutbecher, Alexandra Subklewe, Marion Dick, Andrea Zange, Sabine Girl, Philipp Müller, Katharina Weigert, Oliver Hopfner, Karl-Peter Stemmler, Hans-Joachim von Bergwelt-Baildon, Michael Keppler, Oliver T. Wölfel, Roman Muenchhoff, Maximilian Moosmann, Andreas Nat Commun Article Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design. Nature Publishing Group UK 2022-09-23 /pmc/articles/PMC9508331/ /pubmed/36151076 http://dx.doi.org/10.1038/s41467-022-32772-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Khatamzas, Elham
Antwerpen, Markus H.
Rehn, Alexandra
Graf, Alexander
Hellmuth, Johannes Christian
Hollaus, Alexandra
Mohr, Anne-Wiebe
Gaitzsch, Erik
Weiglein, Tobias
Georgi, Enrico
Scherer, Clemens
Stecher, Stephanie-Susanne
Gruetzner, Stefanie
Blum, Helmut
Krebs, Stefan
Reischer, Anna
Leutbecher, Alexandra
Subklewe, Marion
Dick, Andrea
Zange, Sabine
Girl, Philipp
Müller, Katharina
Weigert, Oliver
Hopfner, Karl-Peter
Stemmler, Hans-Joachim
von Bergwelt-Baildon, Michael
Keppler, Oliver T.
Wölfel, Roman
Muenchhoff, Maximilian
Moosmann, Andreas
Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
title Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
title_full Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
title_fullStr Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
title_full_unstemmed Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
title_short Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
title_sort accumulation of mutations in antibody and cd8 t cell epitopes in a b cell depleted lymphoma patient with chronic sars-cov-2 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508331/
https://www.ncbi.nlm.nih.gov/pubmed/36151076
http://dx.doi.org/10.1038/s41467-022-32772-5
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