Academic Journal
SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display.
| Title: | SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display. |
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| Authors: | Ehling RA; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Weber CR; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; deepCDR Biologics AG, Basel, Switzerland., Mason DM; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; deepCDR Biologics AG, Basel, Switzerland., Friedensohn S; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; deepCDR Biologics AG, Basel, Switzerland., Wagner B; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Bieberich F; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Kapetanovic E; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Vazquez-Lombardi R; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Di Roberto RB; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Hong KL; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; Botnar Research Centre for Child Health, Basel, Switzerland., Wagner C; deepCDR Biologics AG, Basel, Switzerland., Pataia M; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; deepCDR Biologics AG, Basel, Switzerland., Overath MD; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Sheward DJ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Murrell B; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Yermanos A; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; Botnar Research Centre for Child Health, Basel, Switzerland; Institute of Microbiology and Immunology, Department of Biology, ETH Zurich, Zurich, Switzerland; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Cuny AP; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; Swiss Institute of Bioinformatics, Mattenstr. 26, 4058 Basel, Switzerland., Savic M; Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland; Department of Surgery, Oral and Cranio-Maxillofacial Surgery, University Hospital Basel, Basel, Switzerland; Department of Health, Economics and Health Directorate, Canton Basel-Landschaft, Switzerland., Rudolf F; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; Swiss Institute of Bioinformatics, Mattenstr. 26, 4058 Basel, Switzerland., Reddy ST; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; Botnar Research Centre for Child Health, Basel, Switzerland. Electronic address: sai.reddy@ethz.ch. |
| Source: | Cell reports [Cell Rep] 2022 Jan 18; Vol. 38 (3), pp. 110242. Date of Electronic Publication: 2021 Dec 22. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| MeSH Terms: | Antibodies, Neutralizing/*isolation & purification , Plasma Cells/*metabolism , SARS-CoV-2/*immunology , Single-Cell Analysis/*methods, Animals ; Antibodies, Viral/isolation & purification ; COVID-19/immunology ; COVID-19/prevention & control ; Cells, Cultured ; Cohort Studies ; Gene Library ; HEK293 Cells ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Mammals ; Neutralization Tests ; Peptide Library ; Plasma Cells/chemistry |
| Abstract: | Characterization of COVID-19 antibodies has largely focused on memory B cells; however, it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in resolving SARS-CoV-2 infection. Little is known about the specificity of plasma cells, largely because plasma cells lack surface antibody expression, thereby complicating their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and mammalian display to interrogate the specificity of plasma cells from 16 convalescent patients. Single-cell sequencing allows us to profile antibody repertoire features and identify expanded clonal lineages. Mammalian display screening is used to reveal that 43 antibodies (of 132 candidates) derived from expanded plasma cell lineages are specific to SARS-CoV-2 antigens, including antibodies with high affinity to the SARS-CoV-2 receptor-binding domain (RBD) that exhibit potent neutralization and broad binding to the RBD of SARS-CoV-2 variants (of concern/interest). Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.) |
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| Contributed Indexing: | Keywords: B cell; COVID-19; CRISPR; SARS-CoV-2; VoC; antibody; antibody repertoire; mammalian display; plasma cell; single-cell sequencing |
| Substance Nomenclature: | 0 (Antibodies, Neutralizing) 0 (Antibodies, Viral) 0 (Peptide Library) |
| Entry Date(s): | Date Created: 20220109 Date Completed: 20220127 Latest Revision: 20220127 |
| Update Code: | 20221216 |
| PubMed Central ID: | PMC8692065 |
| DOI: | 10.1016/j.celrep.2021.110242 |
| PMID: | 34998467 |
| Database: | MEDLINE |
Accede al texto completo | ISSN: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2021.110242 |