Neutralizing antibodies targeting the SARS-CoV-2 receptor binding domain isolated from a naïve human antibody library
© 2021 The Protein Society..
Infection with SARS-CoV-2 elicits robust antibody responses in some patients, with a majority of the response directed at the receptor binding domain (RBD) of the spike surface glycoprotein. Remarkably, many patient-derived antibodies that potently inhibit viral infection harbor few to no mutations from the germline, suggesting that naïve antibody libraries are a viable means for discovery of novel SARS-CoV-2 neutralizing antibodies. Here, we used a yeast surface-display library of human naïve antibodies to isolate and characterize three novel neutralizing antibodies that target the RBD: one that blocks interaction with angiotensin-converting enzyme 2 (ACE2), the human receptor for SARS-CoV-2, and two that target other epitopes on the RBD. These three antibodies neutralized SARS-CoV-2 spike-pseudotyped lentivirus with IC50 values as low as 60 ng/ml in vitro. Using a biolayer interferometry-based binding competition assay, we determined that these antibodies have distinct but overlapping epitopes with antibodies elicited during natural COVID-19 infection. Taken together, these analyses highlight how in vitro selection of naïve antibodies can mimic the humoral response in vivo, yielding neutralizing antibodies and various epitopes that can be effectively targeted on the SARS-CoV-2 RBD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Protein science : a publication of the Protein Society - 30(2021), 4 vom: 06. Apr., Seite 716-727 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bell, Benjamin N [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.04.2021 Date Revised 06.04.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/pro.4044 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM321459156 |
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| 245 | 1 | 0 | |a Neutralizing antibodies targeting the SARS-CoV-2 receptor binding domain isolated from a naïve human antibody library |
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| 500 | |a Date Revised 06.04.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Protein Society. | ||
| 520 | |a Infection with SARS-CoV-2 elicits robust antibody responses in some patients, with a majority of the response directed at the receptor binding domain (RBD) of the spike surface glycoprotein. Remarkably, many patient-derived antibodies that potently inhibit viral infection harbor few to no mutations from the germline, suggesting that naïve antibody libraries are a viable means for discovery of novel SARS-CoV-2 neutralizing antibodies. Here, we used a yeast surface-display library of human naïve antibodies to isolate and characterize three novel neutralizing antibodies that target the RBD: one that blocks interaction with angiotensin-converting enzyme 2 (ACE2), the human receptor for SARS-CoV-2, and two that target other epitopes on the RBD. These three antibodies neutralized SARS-CoV-2 spike-pseudotyped lentivirus with IC50 values as low as 60 ng/ml in vitro. Using a biolayer interferometry-based binding competition assay, we determined that these antibodies have distinct but overlapping epitopes with antibodies elicited during natural COVID-19 infection. Taken together, these analyses highlight how in vitro selection of naïve antibodies can mimic the humoral response in vivo, yielding neutralizing antibodies and various epitopes that can be effectively targeted on the SARS-CoV-2 RBD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a RBD | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a neutralizing antibody | |
| 650 | 4 | |a yeast surface display | |
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| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
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| 700 | 1 | |a Powell, Abigail E |e verfasserin |4 aut | |
| 700 | 1 | |a Rodriguez, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Cochran, Jennifer R |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Peter S |e verfasserin |4 aut | |
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