Landscape of human antibody recognition of the SARS-CoV-2 receptor binding domain

被引：23

作者：

Wheatley, Adam K. ^{[1
,2
]}

Pymm, Phillip ^{[3
,4
]}

Esterbauer, Robyn ^{[1
]}

Dietrich, Melanie H. ^{[3
,4
]}

Lee, Wen Shi ^{[1
]}

Drew, Damien ^{[3
,4
]}

Kelly, Hannah G. ^{[1
]}

Chan, Li-Jin ^{[3
,4
]}

Mordant, Francesca L. ^{[1
]}

Black, Katrina A. ^{[3
,4
]}

Adair, Amy ^{[3
]}

Tan, Hyon-Xhi ^{[1
]}

Juno, Jennifer A. ^{[1
]}

Wragg, Kathleen M. ^{[1
]}

Amarasena, Thakshila ^{[1
]}

Lopez, Ester ^{[1
]}

Selva, Kevin J. ^{[1
]}

Haycroft, Ebene R. ^{[1
]}

Cooney, James P. ^{[3
,4
]}

Venugopal, Hariprasad ^{[5
]}

Tan, Li Lynn ^{[3
]}

Neill, Matthew T. O. ^{[3
]}

Allison, Cody C. ^{[3
,4
]}

Cromer, Deborah ^{[6
]}

Davenport, Miles P. ^{[6
]}

Bowen, Richard A. ^{[7
]}

Chung, Amy W. ^{[1
]}

Pellegrini, Marc ^{[3
,4
]}

Liddament, Mark T. ^{[8
]}

Glukhova, Alisa ^{[3
,4
,9
,10
]}

Subbarao, Kanta ^{[1
,11
]}

Kent, Stephen J. ^{[1
,2
,12
,13
,14
]}

Tham, Wai-Hong ^{[3
,4
]}

机构：

[1] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic 3000, Australia

[2] Univ Melbourne, Australian Res Council Ctr Excellence Convergent, Melbourne, Vic 3010, Australia

[3] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia

[4] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia

[5] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

[6] Univ New South Wales, Kirby Inst, Kensington, NSW 2052, Australia

[7] Colorado State Univ, Lab Anim Reprod & Biotechnol, Ft Collins, CO 80523 USA

[8] CSL Ltd, Parkville, Vic 3052, Australia

[9] Monash Univ, Monash Fac Pharm & Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia

[10] Univ Melbourne, Dept Biochem & Pharmacol, Melbourne, Vic 3010, Australia

[11] WHO Collaborating Ctr Reference & Res Influenza, Peter Doherty Inst Infect & Immun, 792 Elizabeth St, Melbourne, Vic 3000, Australia

[12] Monash Univ, Melbourne Sexual Hlth Ctr, Alfred Hosp, Melbourne, Vic 3004, Australia

[13] Monash Univ, Dept Infect Dis, Alfred Hosp, Melbourne, Vic 3004, Australia

[14] Monash Univ, Cent Clin Sch, Melbourne, Vic 3004, Australia

来源：

CELL REPORTS | 2021年 / 37卷 / 02期

基金：

澳大利亚国家健康与医学研究理事会; 英国惠康基金;

关键词：

NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; B-CELLS; SPIKE; POTENT;

D O I：

10.1016/j.celrep.2021.109822

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Potent neutralizing monoclonal antibodies are one of the few agents currently available to treat COVID-19. SARS-CoV-2 variants of concern (VOCs) that carry multiple mutations in the viral spike protein can exhibit neutralization resistance, potentially affecting the effectiveness of some antibody-based therapeutics. Here, the generation of a diverse panel of 91 human, neutralizing monoclonal antibodies provides an in-depth structural and phenotypic definition of receptor binding domain (RBD) antigenic sites on the viral spike. These RBD antibodies ameliorate SARS-CoV-2 infection in mice and hamster models in a dose-dependent manner and in proportion to in vitro, neutralizing potency. Assessing the effect of mutations in the spike protein on antibody recognition and neutralization highlights both potent single antibodies and stereotypic classes of antibodies that are unaffected by currently circulating VOCs, such as B.1.351 and P.1. These neutralizing monoclonal antibodies and others that bind analogous epitopes represent potentially useful future anti-SARS-CoV-2 therapeutics.

引用

页数：25

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