Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents
Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Emerging microbes & infections - 13(2024), 1 vom: 15. Jan., Seite 2290841 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yan, Qihong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.01.2024 Date Revised 27.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/22221751.2023.2290841 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM365358444 |
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| 245 | 1 | 0 | |a Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents |
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| 520 | |a Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a antibody repertoire | |
| 650 | 4 | |a antibodyomics | |
| 650 | 4 | |a epitope mapping | |
| 650 | 4 | |a lineage tracking | |
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| 700 | 1 | |a Zhang, Yudi |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Ruitian |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Wenjing |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Xijie |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Weiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiaohan |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Linbing |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Congli |e verfasserin |4 aut | |
| 700 | 1 | |a He, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Banghui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xinwei |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Zihan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhaoming |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Pingchao |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Xiaoli |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Song |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Xuefeng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ling |e verfasserin |4 aut | |
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