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

被引：7

作者：

Westendorf, Kathryn ^{[1
]}

Zentelis, Stefanie ^{[1
]}

Wang, Lingshu ^{[2
]}

Foster, Denisa ^{[3
]}

Vaillancourt, Peter ^{[3
]}

Wiggin, Matthew ^{[1
]}

Lovett, Erica ^{[1
]}

van der Lee, Robin ^{[1
]}

Hendle, Joerg ^{[3
]}

Pustilnik, Anna ^{[3
]}

Sauder, J. Michael ^{[3
]}

Kraft, Lucas ^{[1
]}

Hwang, Yuri ^{[1
]}

Siegel, Robert W. ^{[4
]}

Chen, Jinbiao ^{[4
]}

Heinz, Beverly A. ^{[4
]}

Higgs, Richard E. ^{[4
]}

Kallewaard, Nicole L. ^{[4
]}

Jepson, Kevin ^{[1
]}

Goya, Rodrigo ^{[1
]}

Smith, Maia A. ^{[1
]}

Collins, David W. ^{[1
]}

Pellacani, Davide ^{[1
]}

Xiang, Ping ^{[1
]}

de Puyraimond, Valentine ^{[1
]}

Ricicova, Marketa ^{[1
]}

Devorkin, Lindsay ^{[1
]}

Pritchard, Caitlin ^{[1
]}

O'Neill, Aoise ^{[1
]}

Dalal, Kush ^{[1
]}

Panwar, Pankaj ^{[1
]}

Dhupar, Harveer ^{[1
]}

Garces, Fabian A. ^{[1
]}

Cohen, Courtney A. ^{[5
]}

Dye, John M. ^{[5
]}

Huie, Kathleen E. ^{[5
]}

V. Badger, Catherine ^{[5
]}

Kobasa, Darwyn ^{[6
,7
]}

Audet, Jonathan ^{[6
,7
]}

Freitas, Joshua J. ^{[3
]}

Hassanali, Saleema ^{[3
]}

Hughes, Ina ^{[3
]}

Munoz, Luis ^{[3
]}

Palma, Holly C. ^{[3
]}

Ramamurthy, Bharathi ^{[3
]}

Cross, Robert W. ^{[7
,8
,9
]}

Geisbert, Thomas W. ^{[7
,8
,9
]}

Menachery, Vineet ^{[8
,9
]}

Lokugamage, Kumari ^{[8
,9
]}

Borisevich, Viktoriya ^{[8
]}

机构：

[1] AbCellera Biol Inc, Vancouver, BC V5Y 0A1, Canada

[2] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[3] Eli Lilly & Co, Lilly Biotechnol Ctr, San Diego, CA 92121 USA

[4] Eli Lilly & Co, Indianapolis, IN 46285 USA

[5] US Army Med Res Inst Infect Dis USAMRIID, Frederick, MD 21702 USA

[6] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB R3E 3L5, Canada

[7] Univ Manitoba, Winnipeg, MB R3T 2N2, Canada

[8] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA

[9] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

来源：

CELL REPORTS | 2022年 / 39卷 / 07期

基金：

欧盟地平线“2020”;

关键词：

VALIDATION; IMMUNITY;

D O I：

10.1016/j.celrep.2022.110812

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. LYCoV1404 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.

引用

页数：26

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