Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV ‐2
Antiviral monoclonal antibody (mAb) discovery enables the development of antibody-based antiviral therapeutics. Traditional antiviral mAb discovery relies on affinity between antibody and a viral antigen to discover potent neutralizing antibodies, but these approaches are inefficient because many hi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022
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| Online Access: | https://hdl.handle.net/1721.1/140317 |
| _version_ | 1826202576828235776 |
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| author | Madan, Bharat Reddem, Eswar R. Wang, Pengfei Casner, Ryan G. Nair, Manoj S. Huang, Yaoxing Fahad, Ahmed S. Souza, Matheus Oliveira Banach, Bailey B. López Acevedo, Sheila N. Pan, Xiaoli Nimrania, Rajani Teng, I‐Ting Bahna, Fabiana Zhou, Tongqing Zhang, Baoshan Yin, Michael T. Ho, David D. Kwong, Peter D. Shapiro, Lawrence DeKosky, Brandon J. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Madan, Bharat Reddem, Eswar R. Wang, Pengfei Casner, Ryan G. Nair, Manoj S. Huang, Yaoxing Fahad, Ahmed S. Souza, Matheus Oliveira Banach, Bailey B. López Acevedo, Sheila N. Pan, Xiaoli Nimrania, Rajani Teng, I‐Ting Bahna, Fabiana Zhou, Tongqing Zhang, Baoshan Yin, Michael T. Ho, David D. Kwong, Peter D. Shapiro, Lawrence DeKosky, Brandon J. |
| author_sort | Madan, Bharat |
| collection | MIT |
| description | Antiviral monoclonal antibody (mAb) discovery enables the development of antibody-based antiviral therapeutics. Traditional antiviral mAb discovery relies on affinity between antibody and a viral antigen to discover potent neutralizing antibodies, but these approaches are inefficient because many high affinity mAbs have no neutralizing activity. We sought to determine whether screening for anti-SARS-CoV-2 mAbs at reduced pH could provide more efficient neutralizing antibody discovery. We mined the antibody response of a convalescent COVID-19 patient at both physiological pH (7.4) and reduced pH (4.5), revealing that SARS-CoV-2 neutralizing antibodies were preferentially enriched in pH 4.5 yeast display sorts. Structural analysis revealed that a potent new antibody called LP5 targets the SARS-CoV-2 N-terminal domain supersite via a unique binding recognition mode. Our data combine with evidence from prior studies to support antibody screening at pH 4.5 to accelerate antiviral neutralizing antibody discovery. |
| first_indexed | 2024-09-23T12:09:49Z |
| format | Article |
| id | mit-1721.1/140317 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:09:49Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1403172023-04-07T20:37:21Z Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV ‐2 Madan, Bharat Reddem, Eswar R. Wang, Pengfei Casner, Ryan G. Nair, Manoj S. Huang, Yaoxing Fahad, Ahmed S. Souza, Matheus Oliveira Banach, Bailey B. López Acevedo, Sheila N. Pan, Xiaoli Nimrania, Rajani Teng, I‐Ting Bahna, Fabiana Zhou, Tongqing Zhang, Baoshan Yin, Michael T. Ho, David D. Kwong, Peter D. Shapiro, Lawrence DeKosky, Brandon J. Massachusetts Institute of Technology. Department of Chemical Engineering Antiviral monoclonal antibody (mAb) discovery enables the development of antibody-based antiviral therapeutics. Traditional antiviral mAb discovery relies on affinity between antibody and a viral antigen to discover potent neutralizing antibodies, but these approaches are inefficient because many high affinity mAbs have no neutralizing activity. We sought to determine whether screening for anti-SARS-CoV-2 mAbs at reduced pH could provide more efficient neutralizing antibody discovery. We mined the antibody response of a convalescent COVID-19 patient at both physiological pH (7.4) and reduced pH (4.5), revealing that SARS-CoV-2 neutralizing antibodies were preferentially enriched in pH 4.5 yeast display sorts. Structural analysis revealed that a potent new antibody called LP5 targets the SARS-CoV-2 N-terminal domain supersite via a unique binding recognition mode. Our data combine with evidence from prior studies to support antibody screening at pH 4.5 to accelerate antiviral neutralizing antibody discovery. 2022-02-14T16:53:01Z 2022-02-14T16:53:01Z 2021-10-04 Article http://purl.org/eprint/type/JournalArticle 0001-1541 1547-5905 https://hdl.handle.net/1721.1/140317 Madan, Bharat, Reddem, Eswar R., Wang, Pengfei, Casner, Ryan G., Nair, Manoj S. et al. 2021. "Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV ‐2." AIChE Journal, 67 (12). en http://dx.doi.org/10.1002/aic.17440 AIChE Journal Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Wiley |
| spellingShingle | Madan, Bharat Reddem, Eswar R. Wang, Pengfei Casner, Ryan G. Nair, Manoj S. Huang, Yaoxing Fahad, Ahmed S. Souza, Matheus Oliveira Banach, Bailey B. López Acevedo, Sheila N. Pan, Xiaoli Nimrania, Rajani Teng, I‐Ting Bahna, Fabiana Zhou, Tongqing Zhang, Baoshan Yin, Michael T. Ho, David D. Kwong, Peter D. Shapiro, Lawrence DeKosky, Brandon J. Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV ‐2 |
| title | Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV ‐2 |
| title_full | Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV ‐2 |
| title_fullStr | Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV ‐2 |
| title_full_unstemmed | Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV ‐2 |
| title_short | Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV ‐2 |
| title_sort | antibody screening at reduced ph enables preferential selection of potently neutralizing antibodies targeting sars cov 2 |
| url | https://hdl.handle.net/1721.1/140317 |
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