Cell Reports (May 2022)
LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants
- 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
Affiliations
- Kathryn Westendorf
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Stefanie Žentelis
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Lingshu Wang
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Denisa Foster
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- Peter Vaillancourt
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- Matthew Wiggin
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Erica Lovett
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Robin van der Lee
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Jörg Hendle
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- Anna Pustilnik
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- J. Michael Sauder
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- Lucas Kraft
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Yuri Hwang
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Robert W. Siegel
- Eli Lilly and Company, Indianapolis, IN 46285, USA
- Jinbiao Chen
- Eli Lilly and Company, Indianapolis, IN 46285, USA
- Beverly A. Heinz
- Eli Lilly and Company, Indianapolis, IN 46285, USA
- Richard E. Higgs
- Eli Lilly and Company, Indianapolis, IN 46285, USA
- Nicole L. Kallewaard
- Eli Lilly and Company, Indianapolis, IN 46285, USA
- Kevin Jepson
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Rodrigo Goya
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Maia A. Smith
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- David W. Collins
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Davide Pellacani
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Ping Xiang
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Valentine de Puyraimond
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Marketa Ricicova
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Lindsay Devorkin
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Caitlin Pritchard
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Aoise O’Neill
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Kush Dalal
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Pankaj Panwar
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Harveer Dhupar
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Fabian A. Garces
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Courtney A. Cohen
- U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA
- John M. Dye
- U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA
- Kathleen E. Huie
- U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA
- Catherine V. Badger
- U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA
- Darwyn Kobasa
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3L5, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, Canada
- Jonathan Audet
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3L5, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, Canada
- Joshua J. Freitas
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- Saleema Hassanali
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- Ina Hughes
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- Luis Munoz
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- Holly C. Palma
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- Bharathi Ramamurthy
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA
- Robert W. Cross
- University 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, USA
- Thomas W. Geisbert
- University 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, USA
- Vineet Menachery
- 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, USA
- Kumari Lokugamage
- 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, USA
- Viktoriya Borisevich
- 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, USA
- Iliana Lanz
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Lisa Anderson
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Payal Sipahimalani
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Kizzmekia S. Corbett
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Eun Sung Yang
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Yi Zhang
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Wei Shi
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Tongqing Zhou
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Misook Choe
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- John Misasi
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Peter D. Kwong
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Nancy J. Sullivan
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Barney S. Graham
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Tara L. Fernandez
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Carl L. Hansen
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- Ester Falconer
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada
- John R. Mascola
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Bryan E. Jones
- Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA; Corresponding author
- Bryan C. Barnhart
- AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada; Corresponding author
- Journal volume & issue
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Vol. 39,
no. 7
p. 110812
Abstract
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.
