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

doi:10.1016/j.celrep.2022.110812

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 GoyaMaia 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

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

260 Scopus citations

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.

Original language	English (US)
Article number	110812
Journal	Cell Reports
Volume	39
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2022.110812
State	Published - May 17 2022

Keywords

COVID-19
CP: Microbiology
SARS-CoV-2
neutralizing antibody
variant of concern

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2022.110812

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Westendorf, K., Žentelis, S., Wang, L., Foster, D., Vaillancourt, P., Wiggin, M., Lovett, E., van der Lee, R., Hendle, J., Pustilnik, A., Sauder, J. M., Kraft, L., Hwang, Y., Siegel, R. W., Chen, J., Heinz, B. A., Higgs, R. E., Kallewaard, N. L., Jepson, K., ... Barnhart, B. C. (2022). LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants. Cell Reports, 39(7), Article 110812. https://doi.org/10.1016/j.celrep.2022.110812

Westendorf, K, Žentelis, S, Wang, L, Foster, D, Vaillancourt, P, Wiggin, M, Lovett, E, van der Lee, R, Hendle, J, Pustilnik, A, Sauder, JM, Kraft, L, Hwang, Y, Siegel, RW, Chen, J, Heinz, BA, Higgs, RE, Kallewaard, NL, Jepson, K, Goya, R, Smith, MA, Collins, DW, Pellacani, D, Xiang, P, de Puyraimond, V, Ricicova, M, Devorkin, L, Pritchard, C, O'Neill, A, Dalal, K, Panwar, P, Dhupar, H, Garces, FA, Cohen, CA, Dye, JM, Huie, KE, Badger, CV, Kobasa, D, Audet, J, Freitas, JJ, Hassanali, S, Hughes, I, Munoz, L, Palma, HC, Ramamurthy, B, Cross, RW , Geisbert, TW, Menachery, V, Lokugamage, K, Borisevich, V, Lanz, I, Anderson, L, Sipahimalani, P, Corbett, KS, Yang, ES, Zhang, Y, Shi, W, Zhou, T, Choe, M, Misasi, J, Kwong, PD, Sullivan, NJ, Graham, BS, Fernandez, TL, Hansen, CL, Falconer, E, Mascola, JR, Jones, BE & Barnhart, BC 2022, 'LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants', Cell Reports, vol. 39, no. 7, 110812. https://doi.org/10.1016/j.celrep.2022.110812

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title = "LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants",

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",

author = "Kathryn Westendorf and Stefanie {\v Z}entelis and Lingshu Wang and Denisa Foster and Peter Vaillancourt and Matthew Wiggin and Erica Lovett and {van der Lee}, Robin and J{\"o}rg Hendle and Anna Pustilnik and Sauder, {J. Michael} and Lucas Kraft and Yuri Hwang and Siegel, {Robert W.} and Jinbiao Chen and Heinz, {Beverly A.} and Higgs, {Richard E.} and Kallewaard, {Nicole L.} and Kevin Jepson and Rodrigo Goya and Smith, {Maia A.} and Collins, {David W.} and Davide Pellacani and Ping Xiang and {de Puyraimond}, Valentine and Marketa Ricicova and Lindsay Devorkin and Caitlin Pritchard and Aoise O'Neill and Kush Dalal and Pankaj Panwar and Harveer Dhupar and Garces, {Fabian A.} and Cohen, {Courtney A.} and Dye, {John M.} and Huie, {Kathleen E.} and Badger, {Catherine V.} and Darwyn Kobasa and Jonathan Audet and Freitas, {Joshua J.} and Saleema Hassanali and Ina Hughes and Luis Munoz and Palma, {Holly C.} and Bharathi Ramamurthy and Cross, {Robert W.} and Geisbert, {Thomas W.} and Vineet Menachery and Kumari Lokugamage and Viktoriya Borisevich and Iliana Lanz and Lisa Anderson and Payal Sipahimalani and Corbett, {Kizzmekia S.} and Yang, {Eun Sung} and Yi Zhang and Wei Shi and Tongqing Zhou and Misook Choe and John Misasi and Kwong, {Peter D.} and Sullivan, {Nancy J.} and Graham, {Barney S.} and Fernandez, {Tara L.} and Hansen, {Carl L.} and Ester Falconer and Mascola, {John R.} and Jones, {Bryan E.} and Barnhart, {Bryan C.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = may,

day = "17",

doi = "10.1016/j.celrep.2022.110812",

language = "English (US)",

volume = "39",

journal = "Cell Reports",

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T1 - LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants

AU - Westendorf, Kathryn

AU - Žentelis, Stefanie

AU - Wang, Lingshu

AU - Foster, Denisa

AU - Vaillancourt, Peter

AU - Wiggin, Matthew

AU - Lovett, Erica

AU - van der Lee, Robin

AU - Hendle, Jörg

AU - Pustilnik, Anna

AU - Sauder, J. Michael

AU - Kraft, Lucas

AU - Hwang, Yuri

AU - Siegel, Robert W.

AU - Chen, Jinbiao

AU - Heinz, Beverly A.

AU - Higgs, Richard E.

AU - Kallewaard, Nicole L.

AU - Jepson, Kevin

AU - Goya, Rodrigo

AU - Smith, Maia A.

AU - Collins, David W.

AU - Pellacani, Davide

AU - Xiang, Ping

AU - de Puyraimond, Valentine

AU - Ricicova, Marketa

AU - Devorkin, Lindsay

AU - Pritchard, Caitlin

AU - O'Neill, Aoise

AU - Dalal, Kush

AU - Panwar, Pankaj

AU - Dhupar, Harveer

AU - Garces, Fabian A.

AU - Cohen, Courtney A.

AU - Dye, John M.

AU - Huie, Kathleen E.

AU - Badger, Catherine V.

AU - Kobasa, Darwyn

AU - Audet, Jonathan

AU - Freitas, Joshua J.

AU - Hassanali, Saleema

AU - Hughes, Ina

AU - Munoz, Luis

AU - Palma, Holly C.

AU - Ramamurthy, Bharathi

AU - Cross, Robert W.

AU - Geisbert, Thomas W.

AU - Menachery, Vineet

AU - Lokugamage, Kumari

AU - Borisevich, Viktoriya

AU - Lanz, Iliana

AU - Anderson, Lisa

AU - Sipahimalani, Payal

AU - Corbett, Kizzmekia S.

AU - Yang, Eun Sung

AU - Zhang, Yi

AU - Shi, Wei

AU - Zhou, Tongqing

AU - Choe, Misook

AU - Misasi, John

AU - Kwong, Peter D.

AU - Sullivan, Nancy J.

AU - Graham, Barney S.

AU - Fernandez, Tara L.

AU - Hansen, Carl L.

AU - Falconer, Ester

AU - Mascola, John R.

AU - Jones, Bryan E.

AU - Barnhart, Bryan C.

PY - 2022/5/17

Y1 - 2022/5/17

N2 - 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.

AB - 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.

KW - COVID-19

KW - CP: Microbiology

KW - SARS-CoV-2

KW - neutralizing antibody

KW - variant of concern

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AN - SCOPUS:85130359181

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VL - 39

JO - Cell Reports

JF - Cell Reports

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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