LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants.

Autor:	Westendorf K; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Žentelis S; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Wang L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Foster D; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Vaillancourt P; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Wiggin M; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Lovett E; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., van der Lee R; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Hendle J; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Pustilnik A; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Sauder JM; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Kraft L; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Hwang Y; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Siegel RW; Eli Lilly and Company, Indianapolis, IN 46285, USA., Chen J; Eli Lilly and Company, Indianapolis, IN 46285, USA., Heinz BA; Eli Lilly and Company, Indianapolis, IN 46285, USA., Higgs RE; Eli Lilly and Company, Indianapolis, IN 46285, USA., Kallewaard NL; Eli Lilly and Company, Indianapolis, IN 46285, USA., Jepson K; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Goya R; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Smith MA; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Collins DW; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Pellacani D; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Xiang P; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., de Puyraimond V; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Ricicova M; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Devorkin L; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Pritchard C; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., O'Neill A; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Dalal K; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Panwar P; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Dhupar H; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Garces FA; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Cohen CA; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA., Dye JM; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA., Huie KE; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA., Badger CV; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA., Kobasa D; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3L5, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, Canada., Audet J; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3L5, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, Canada., Freitas JJ; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Hassanali S; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Hughes I; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Munoz L; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Palma HC; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Ramamurthy B; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Cross RW; 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., Geisbert TW; 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., Menachery V; 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., Lokugamage K; 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., Borisevich V; 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., Lanz I; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Anderson L; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Sipahimalani P; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Corbett KS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Yang ES; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Zhang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Shi W; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Choe M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Misasi J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Sullivan NJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Graham BS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Fernandez TL; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Hansen CL; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Falconer E; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada., Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Jones BE; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA. Electronic address: jones_bryan_edward@lilly.com., Barnhart BC; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada. Electronic address: bo.barnhart@abcellera.com.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 May 17; Vol. 39 (7), pp. 110812. Date of Electronic Publication: 2022 Apr 25.
DOI:	10.1016/j.celrep.2022.110812
Abstrakt:	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. Competing Interests: Declaration of interests Eli Lilly and Company provided resources for this study. AbCellera Biologics Inc. received funding from the U.S. Department of Defense, Defense Advanced Research Projects Agency (DARPA) Pandemic Prevention Platform, agreement D18AC00002. This research was funded in part by the U.S. Government (the views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the U.S. Government). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under contract DE-AC02-06CH11357 (https://www.aps.anl.gov/Science/Publications/Acknowledgment-Statement-for-Publications). Use of the Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beamline at Sector 31 of the Advanced Photon Source was provided by Eli Lilly and Company, which operates the facility (http://lrlcat.lilly.com/). This work was supported by the Intramural Program at the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center (to B.S.G. and J.R.M.). Operations support of the Galveston National Laboratory was supported by NIAID/NIH grant UC7AI094660. D.F., P.V., A.P., J.H., J.M.S., R.W.S., J.C., I. H., J.J.F., S.H., H.C.P., B.R., B.A.H., R.W.S., J.C., J.M.S., R.E.H., N.K., and B.E.J. are employees and/or stockholders of Eli Lilly and Company. K.W., S.Ž., M.W., E.L., L.K., Y.H., K.J., R.G., M.A.S., D.W.C., D.P., P.X., V.d.P., R.v.d.L., M.R., L.D., C.P., I.L., L.A., P.S., T.L.F., C.L.H., E.F., and B.C.B. are employees and stockholders of AbCellera Biologics Inc. AbCellera Biologics Inc. and the National Institutes of Health have filed patent applications related to the work described herein (US patent application 17/192243 and international patent application PCT/US21/20843, both titled “Anti-Coronavirus Antibodies and Methods of Use”). (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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