Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody
Three coronaviruses have spilled over from animal reservoirs into the human population and caused deadly epidemics or pandemics. The continued emergence of coronaviruses highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using LIBRA-seq, we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these antibodies, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryo-EM structure of 54043-5 bound to the pre-fusion S2 subunit of the SARS-CoV-2 spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses, including ADCC and ADCP. In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2024) vom: 16. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Johnson, Nicole V [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 07.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2024.01.15.575741 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367835533 |
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| 100 | 1 | |a Johnson, Nicole V |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody |
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| 500 | |a Date Revised 07.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Three coronaviruses have spilled over from animal reservoirs into the human population and caused deadly epidemics or pandemics. The continued emergence of coronaviruses highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using LIBRA-seq, we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these antibodies, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryo-EM structure of 54043-5 bound to the pre-fusion S2 subunit of the SARS-CoV-2 spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses, including ADCC and ADCP. In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit | ||
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| 700 | 1 | |a Wall, Steven C |e verfasserin |4 aut | |
| 700 | 1 | |a Kramer, Kevin J |e verfasserin |4 aut | |
| 700 | 1 | |a Holt, Clinton M |e verfasserin |4 aut | |
| 700 | 1 | |a Periasamy, Sivakumar |e verfasserin |4 aut | |
| 700 | 1 | |a Richardson, Simone |e verfasserin |4 aut | |
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| 700 | 1 | |a Pierleoni, Giulio |e verfasserin |4 aut | |
| 700 | 1 | |a Piccini, Giulia |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Ge, Pan |e verfasserin |4 aut | |
| 700 | 1 | |a Allen, James D |e verfasserin |4 aut | |
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