Cross-reactive coronavirus antibodies with diverse epitope specificities and extra-neutralization functions
The continual emergence of novel coronavirus (CoV) strains, like SARS-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. Coronavirus spike (S) proteins share common structural motifs that could be vulnerable to cross-reactive antibody responses. To study this phenomenon in human coronavirus infection, we applied a high-throughput sequencing method called LIBRA-seq (Linking B cell receptor to antigen specificity through sequencing) to a SARS-CoV-1 convalescent donor sample. We identified and characterized a panel of six monoclonal antibodies that cross-reacted with S proteins from the highly pathogenic SARS-CoV-1 and SARS-CoV-2 and demonstrated a spectrum of reactivity against other coronaviruses. Epitope mapping revealed that these antibodies recognized multiple epitopes on SARS-CoV-2 S, including the receptor binding domain (RBD), N-terminal domain (NTD), and S2 subunit. Functional characterization demonstrated that the antibodies mediated a variety of Fc effector functions in vitro and mitigated pathological burden in vivo . The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies that may be useful for preventing potential future coronavirus outbreaks.
| Errataetall: |
UpdateIn: Cell Rep Med. 2021 May 21;:100313. - PMID 34056628 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 20. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shiakolas, Andrea R [VerfasserIn] |
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Date Revised 16.06.2021 published: Electronic UpdateIn: Cell Rep Med. 2021 May 21;:100313. - PMID 34056628 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.12.20.414748 |
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| funding: |
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| PPN (Katalog-ID): |
NLM319621766 |
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| 245 | 1 | 0 | |a Cross-reactive coronavirus antibodies with diverse epitope specificities and extra-neutralization functions |
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| 500 | |a Date Revised 16.06.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a UpdateIn: Cell Rep Med. 2021 May 21;:100313. - PMID 34056628 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a The continual emergence of novel coronavirus (CoV) strains, like SARS-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. Coronavirus spike (S) proteins share common structural motifs that could be vulnerable to cross-reactive antibody responses. To study this phenomenon in human coronavirus infection, we applied a high-throughput sequencing method called LIBRA-seq (Linking B cell receptor to antigen specificity through sequencing) to a SARS-CoV-1 convalescent donor sample. We identified and characterized a panel of six monoclonal antibodies that cross-reacted with S proteins from the highly pathogenic SARS-CoV-1 and SARS-CoV-2 and demonstrated a spectrum of reactivity against other coronaviruses. Epitope mapping revealed that these antibodies recognized multiple epitopes on SARS-CoV-2 S, including the receptor binding domain (RBD), N-terminal domain (NTD), and S2 subunit. Functional characterization demonstrated that the antibodies mediated a variety of Fc effector functions in vitro and mitigated pathological burden in vivo . The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies that may be useful for preventing potential future coronavirus outbreaks | ||
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| 700 | 1 | |a Kramer, Kevin J |e verfasserin |4 aut | |
| 700 | 1 | |a Wrapp, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Richardson, Simone I |e verfasserin |4 aut | |
| 700 | 1 | |a Schäfer, Alexandra |e verfasserin |4 aut | |
| 700 | 1 | |a Wall, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Nianshuang |e verfasserin |4 aut | |
| 700 | 1 | |a Janowska, Katarzyna |e verfasserin |4 aut | |
| 700 | 1 | |a Pilewski, Kelsey A |e verfasserin |4 aut | |
| 700 | 1 | |a Venkat, Rohit |e verfasserin |4 aut | |
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| 700 | 1 | |a Manamela, Nelia P |e verfasserin |4 aut | |
| 700 | 1 | |a Raju, Nagarajan |e verfasserin |4 aut | |
| 700 | 1 | |a Fechter, Emilee Friedman |e verfasserin |4 aut | |
| 700 | 1 | |a Holt, Clinton M |e verfasserin |4 aut | |
| 700 | 1 | |a Suryadevara, Naveenchandra |e verfasserin |4 aut | |
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| 700 | 1 | |a Martinez, David R |e verfasserin |4 aut | |
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