LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic...
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124722005836 |
| _version_ | 1828554312983248896 |
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| author | Kathryn Westendorf Stefanie Žentelis Lingshu Wang Denisa Foster Peter Vaillancourt Matthew Wiggin Erica Lovett Robin van der Lee Jörg Hendle Anna Pustilnik J. Michael Sauder Lucas Kraft Yuri Hwang Robert W. Siegel Jinbiao Chen Beverly A. Heinz Richard E. Higgs Nicole L. Kallewaard Kevin Jepson Rodrigo Goya Maia A. Smith David W. Collins Davide Pellacani Ping Xiang Valentine de Puyraimond Marketa Ricicova Lindsay Devorkin Caitlin Pritchard Aoise O’Neill Kush Dalal Pankaj Panwar Harveer Dhupar Fabian A. Garces Courtney A. Cohen John M. Dye Kathleen E. Huie Catherine V. Badger Darwyn Kobasa Jonathan Audet Joshua J. Freitas Saleema Hassanali Ina Hughes Luis Munoz Holly C. Palma Bharathi Ramamurthy Robert W. Cross Thomas W. Geisbert Vineet Menachery Kumari Lokugamage Viktoriya Borisevich Iliana Lanz Lisa Anderson Payal Sipahimalani Kizzmekia S. Corbett Eun Sung Yang Yi Zhang Wei Shi Tongqing Zhou Misook Choe John Misasi Peter D. Kwong Nancy J. Sullivan Barney S. Graham Tara L. Fernandez Carl L. Hansen Ester Falconer John R. Mascola Bryan E. Jones Bryan C. Barnhart |
| author_facet | Kathryn Westendorf Stefanie Žentelis Lingshu Wang Denisa Foster Peter Vaillancourt Matthew Wiggin Erica Lovett Robin van der Lee Jörg Hendle Anna Pustilnik J. Michael Sauder Lucas Kraft Yuri Hwang Robert W. Siegel Jinbiao Chen Beverly A. Heinz Richard E. Higgs Nicole L. Kallewaard Kevin Jepson Rodrigo Goya Maia A. Smith David W. Collins Davide Pellacani Ping Xiang Valentine de Puyraimond Marketa Ricicova Lindsay Devorkin Caitlin Pritchard Aoise O’Neill Kush Dalal Pankaj Panwar Harveer Dhupar Fabian A. Garces Courtney A. Cohen John M. Dye Kathleen E. Huie Catherine V. Badger Darwyn Kobasa Jonathan Audet Joshua J. Freitas Saleema Hassanali Ina Hughes Luis Munoz Holly C. Palma Bharathi Ramamurthy Robert W. Cross Thomas W. Geisbert Vineet Menachery Kumari Lokugamage Viktoriya Borisevich Iliana Lanz Lisa Anderson Payal Sipahimalani Kizzmekia S. Corbett Eun Sung Yang Yi Zhang Wei Shi Tongqing Zhou Misook Choe John Misasi Peter D. Kwong Nancy J. Sullivan Barney S. Graham Tara L. Fernandez Carl L. Hansen Ester Falconer John R. Mascola Bryan E. Jones Bryan C. Barnhart |
| author_sort | Kathryn Westendorf |
| collection | DOAJ |
| description | Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic use of some authorized mAbs. Using a high-throughput B cell screening pipeline, we isolated LY-CoV1404 (bebtelovimab), a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody. LY-CoV1404 potently neutralizes authentic SARS-CoV-2, B.1.1.7, B.1.351, and B.1.617.2. In pseudovirus neutralization studies, LY-CoV1404 potently neutralizes variants, including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved, except for N439 and N501. The binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The broad and potent neutralization activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants. |
| first_indexed | 2024-12-12T05:34:41Z |
| format | Article |
| id | doaj.art-daeff3ff2f814504a3643f35bb419fcf |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T05:34:41Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-daeff3ff2f814504a3643f35bb419fcf2022-12-22T00:36:13ZengElsevierCell Reports2211-12472022-05-01397110812LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variantsKathryn Westendorf0Stefanie Žentelis1Lingshu Wang2Denisa Foster3Peter Vaillancourt4Matthew Wiggin5Erica Lovett6Robin van der Lee7Jörg Hendle8Anna Pustilnik9J. Michael Sauder10Lucas Kraft11Yuri Hwang12Robert W. Siegel13Jinbiao Chen14Beverly A. Heinz15Richard E. Higgs16Nicole L. Kallewaard17Kevin Jepson18Rodrigo Goya19Maia A. Smith20David W. Collins21Davide Pellacani22Ping Xiang23Valentine de Puyraimond24Marketa Ricicova25Lindsay Devorkin26Caitlin Pritchard27Aoise O’Neill28Kush Dalal29Pankaj Panwar30Harveer Dhupar31Fabian A. Garces32Courtney A. Cohen33John M. Dye34Kathleen E. Huie35Catherine V. Badger36Darwyn Kobasa37Jonathan Audet38Joshua J. Freitas39Saleema Hassanali40Ina Hughes41Luis Munoz42Holly C. Palma43Bharathi Ramamurthy44Robert W. Cross45Thomas W. Geisbert46Vineet Menachery47Kumari Lokugamage48Viktoriya Borisevich49Iliana Lanz50Lisa Anderson51Payal Sipahimalani52Kizzmekia S. Corbett53Eun Sung Yang54Yi Zhang55Wei Shi56Tongqing Zhou57Misook Choe58John Misasi59Peter D. Kwong60Nancy J. Sullivan61Barney S. Graham62Tara L. Fernandez63Carl L. Hansen64Ester Falconer65John R. Mascola66Bryan E. Jones67Bryan C. Barnhart68AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USALilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USALilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USAAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaLilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USALilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USALilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USAAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaEli Lilly and Company, Indianapolis, IN 46285, USAEli Lilly and Company, Indianapolis, IN 46285, USAEli Lilly and Company, Indianapolis, IN 46285, USAEli Lilly and Company, Indianapolis, IN 46285, USAEli Lilly and Company, Indianapolis, IN 46285, USAAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaU.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USAU.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USAU.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USAU.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USANational Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3L5, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, CanadaNational Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3L5, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, CanadaLilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USALilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USALilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USALilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USALilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USALilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USAUniversity of Manitoba, Winnipeg, MB R3T 2N2, Canada; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAUniversity of Manitoba, Winnipeg, MB R3T 2N2, Canada; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAGalveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAGalveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAGalveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, CanadaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USALilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA; Corresponding authorAbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada; Corresponding authorSummary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic use of some authorized mAbs. Using a high-throughput B cell screening pipeline, we isolated LY-CoV1404 (bebtelovimab), a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody. LY-CoV1404 potently neutralizes authentic SARS-CoV-2, B.1.1.7, B.1.351, and B.1.617.2. In pseudovirus neutralization studies, LY-CoV1404 potently neutralizes variants, including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved, except for N439 and N501. The binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The broad and potent neutralization activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants.http://www.sciencedirect.com/science/article/pii/S2211124722005836CP: Microbiology |
| spellingShingle | Kathryn Westendorf Stefanie Žentelis Lingshu Wang Denisa Foster Peter Vaillancourt Matthew Wiggin Erica Lovett Robin van der Lee Jörg Hendle Anna Pustilnik J. Michael Sauder Lucas Kraft Yuri Hwang Robert W. Siegel Jinbiao Chen Beverly A. Heinz Richard E. Higgs Nicole L. Kallewaard Kevin Jepson Rodrigo Goya Maia A. Smith David W. Collins Davide Pellacani Ping Xiang Valentine de Puyraimond Marketa Ricicova Lindsay Devorkin Caitlin Pritchard Aoise O’Neill Kush Dalal Pankaj Panwar Harveer Dhupar Fabian A. Garces Courtney A. Cohen John M. Dye Kathleen E. Huie Catherine V. Badger Darwyn Kobasa Jonathan Audet Joshua J. Freitas Saleema Hassanali Ina Hughes Luis Munoz Holly C. Palma Bharathi Ramamurthy Robert W. Cross Thomas W. Geisbert Vineet Menachery Kumari Lokugamage Viktoriya Borisevich Iliana Lanz Lisa Anderson Payal Sipahimalani Kizzmekia S. Corbett Eun Sung Yang Yi Zhang Wei Shi Tongqing Zhou Misook Choe John Misasi Peter D. Kwong Nancy J. Sullivan Barney S. Graham Tara L. Fernandez Carl L. Hansen Ester Falconer John R. Mascola Bryan E. Jones Bryan C. Barnhart LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants Cell Reports CP: Microbiology |
| title | LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants |
| title_full | LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants |
| title_fullStr | LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants |
| title_full_unstemmed | LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants |
| title_short | LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants |
| title_sort | ly cov1404 bebtelovimab potently neutralizes sars cov 2 variants |
| topic | CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124722005836 |
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