tetano
Editor, Senior Moderator
Cell Rep
. 2022 Apr 25;110812.
doi: 10.1016/j.celrep.2022.110812. Online ahead of print.
LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants
Kathryn Westendorf[SUP] 1 [/SUP], Stefanie Žentelis[SUP] 1 [/SUP], Lingshu Wang[SUP] 2 [/SUP], Denisa Foster[SUP] 3 [/SUP], Peter Vaillancourt[SUP] 3 [/SUP], Matthew Wiggin[SUP] 1 [/SUP], Erica Lovett[SUP] 1 [/SUP], Robin van der Lee[SUP] 1 [/SUP], Jörg Hendle[SUP] 3 [/SUP], Anna Pustilnik[SUP] 3 [/SUP], J Michael Sauder[SUP] 3 [/SUP], Lucas Kraft[SUP] 1 [/SUP], Yuri Hwang[SUP] 1 [/SUP], Robert W Siegel[SUP] 4 [/SUP], Jinbiao Chen[SUP] 4 [/SUP], Beverly A Heinz[SUP] 4 [/SUP], Richard E Higgs[SUP] 4 [/SUP], Nicole L Kallewaard[SUP] 4 [/SUP], Kevin Jepson[SUP] 1 [/SUP], Rodrigo Goya[SUP] 1 [/SUP], Maia A Smith[SUP] 1 [/SUP], David W Collins[SUP] 1 [/SUP], Davide Pellacani[SUP] 1 [/SUP], Ping Xiang[SUP] 1 [/SUP], Valentine de Puyraimond[SUP] 1 [/SUP], Marketa Ricicova[SUP] 1 [/SUP], Lindsay Devorkin[SUP] 1 [/SUP], Caitlin Pritchard[SUP] 1 [/SUP], Aoise O'Neill[SUP] 1 [/SUP], Kush Dalal[SUP] 1 [/SUP], Pankaj Panwar[SUP] 1 [/SUP], Harveer Dhupar[SUP] 1 [/SUP], Fabian A Garces[SUP] 1 [/SUP], Courtney A Cohen[SUP] 5 [/SUP], John M Dye[SUP] 5 [/SUP], Kathleen E Huie[SUP] 5 [/SUP], Catherine V Badger[SUP] 5 [/SUP], Darwyn Kobasa[SUP] 6 [/SUP], Jonathan Audet[SUP] 6 [/SUP], Joshua J Freitas[SUP] 3 [/SUP], Saleema Hassanali[SUP] 3 [/SUP], Ina Hughes[SUP] 3 [/SUP], Luis Munoz[SUP] 3 [/SUP], Holly C Palma[SUP] 3 [/SUP], Bharathi Ramamurthy[SUP] 3 [/SUP], Robert W Cross[SUP] 7 [/SUP], Thomas W Geisbert[SUP] 7 [/SUP], Vineet Menachery[SUP] 8 [/SUP], Kumari Lokugamage[SUP] 8 [/SUP], Viktoriya Borisevich[SUP] 8 [/SUP], Iliana Lanz[SUP] 1 [/SUP], Lisa Anderson[SUP] 1 [/SUP], Payal Sipahimalani[SUP] 1 [/SUP], Kizzmekia S Corbett[SUP] 2 [/SUP], Eun Sung Yang[SUP] 2 [/SUP], Yi Zhang[SUP] 2 [/SUP], Wei Shi[SUP] 2 [/SUP], Tongqing Zhou[SUP] 2 [/SUP], Misook Choe[SUP] 2 [/SUP], John Misasi[SUP] 2 [/SUP], Peter D Kwong[SUP] 2 [/SUP], Nancy J Sullivan[SUP] 2 [/SUP], Barney S Graham[SUP] 2 [/SUP], Tara L Fernandez[SUP] 1 [/SUP], Carl L Hansen[SUP] 1 [/SUP], Ester Falconer[SUP] 1 [/SUP], John R Mascola[SUP] 2 [/SUP], Bryan E Jones[SUP] 9 [/SUP], Bryan C Barnhart[SUP] 10 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; CP: Microbiology; SARS-CoV-2; neutralizing antibody; variant of concern.
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
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”).
. 2022 Apr 25;110812.
doi: 10.1016/j.celrep.2022.110812. Online ahead of print.
LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants
Kathryn Westendorf[SUP] 1 [/SUP], Stefanie Žentelis[SUP] 1 [/SUP], Lingshu Wang[SUP] 2 [/SUP], Denisa Foster[SUP] 3 [/SUP], Peter Vaillancourt[SUP] 3 [/SUP], Matthew Wiggin[SUP] 1 [/SUP], Erica Lovett[SUP] 1 [/SUP], Robin van der Lee[SUP] 1 [/SUP], Jörg Hendle[SUP] 3 [/SUP], Anna Pustilnik[SUP] 3 [/SUP], J Michael Sauder[SUP] 3 [/SUP], Lucas Kraft[SUP] 1 [/SUP], Yuri Hwang[SUP] 1 [/SUP], Robert W Siegel[SUP] 4 [/SUP], Jinbiao Chen[SUP] 4 [/SUP], Beverly A Heinz[SUP] 4 [/SUP], Richard E Higgs[SUP] 4 [/SUP], Nicole L Kallewaard[SUP] 4 [/SUP], Kevin Jepson[SUP] 1 [/SUP], Rodrigo Goya[SUP] 1 [/SUP], Maia A Smith[SUP] 1 [/SUP], David W Collins[SUP] 1 [/SUP], Davide Pellacani[SUP] 1 [/SUP], Ping Xiang[SUP] 1 [/SUP], Valentine de Puyraimond[SUP] 1 [/SUP], Marketa Ricicova[SUP] 1 [/SUP], Lindsay Devorkin[SUP] 1 [/SUP], Caitlin Pritchard[SUP] 1 [/SUP], Aoise O'Neill[SUP] 1 [/SUP], Kush Dalal[SUP] 1 [/SUP], Pankaj Panwar[SUP] 1 [/SUP], Harveer Dhupar[SUP] 1 [/SUP], Fabian A Garces[SUP] 1 [/SUP], Courtney A Cohen[SUP] 5 [/SUP], John M Dye[SUP] 5 [/SUP], Kathleen E Huie[SUP] 5 [/SUP], Catherine V Badger[SUP] 5 [/SUP], Darwyn Kobasa[SUP] 6 [/SUP], Jonathan Audet[SUP] 6 [/SUP], Joshua J Freitas[SUP] 3 [/SUP], Saleema Hassanali[SUP] 3 [/SUP], Ina Hughes[SUP] 3 [/SUP], Luis Munoz[SUP] 3 [/SUP], Holly C Palma[SUP] 3 [/SUP], Bharathi Ramamurthy[SUP] 3 [/SUP], Robert W Cross[SUP] 7 [/SUP], Thomas W Geisbert[SUP] 7 [/SUP], Vineet Menachery[SUP] 8 [/SUP], Kumari Lokugamage[SUP] 8 [/SUP], Viktoriya Borisevich[SUP] 8 [/SUP], Iliana Lanz[SUP] 1 [/SUP], Lisa Anderson[SUP] 1 [/SUP], Payal Sipahimalani[SUP] 1 [/SUP], Kizzmekia S Corbett[SUP] 2 [/SUP], Eun Sung Yang[SUP] 2 [/SUP], Yi Zhang[SUP] 2 [/SUP], Wei Shi[SUP] 2 [/SUP], Tongqing Zhou[SUP] 2 [/SUP], Misook Choe[SUP] 2 [/SUP], John Misasi[SUP] 2 [/SUP], Peter D Kwong[SUP] 2 [/SUP], Nancy J Sullivan[SUP] 2 [/SUP], Barney S Graham[SUP] 2 [/SUP], Tara L Fernandez[SUP] 1 [/SUP], Carl L Hansen[SUP] 1 [/SUP], Ester Falconer[SUP] 1 [/SUP], John R Mascola[SUP] 2 [/SUP], Bryan E Jones[SUP] 9 [/SUP], Bryan C Barnhart[SUP] 10 [/SUP]
Affiliations
- PMID: 35568025
- PMCID: PMC9035363
- DOI: 10.1016/j.celrep.2022.110812
Abstract
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.
Keywords: COVID-19; CP: Microbiology; SARS-CoV-2; neutralizing antibody; variant of concern.
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
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”).