The antigenic anatomy of SARS-CoV-2 receptor binding domain

Wanwisa Dejnirattisai; Daming Zhou; Helen M. Ginn; Helen M.E. Duyvesteyn; Piyada Supasa; James Brett Case; Yuguang Zhao; Thomas S. Walter; Alexander J. Mentzer; Chang Liu; Beibei Wang; Guido C. Paesen; Jose Slon-Campos; César López-Camacho; Natasha M. Kafai; Adam L. Bailey; Rita E. Chen; Baoling Ying; Craig Thompson; Jai Bolton; Alex Fyfe; Sunetra Gupta; Tiong Kit Tan; Javier Gilbert-Jaramillo; William James; Michael Knight; Miles W. Carroll; Donal Skelly; Christina Dold; Yanchun Peng; Robert Levin; Tao Dong; Andrew J. Pollard; Julian C. Knight; Paul Klenerman; Nigel Temperton; David R. Hall; Mark A. Williams; Neil G. Paterson; Felicity K.R. Bertram; C. Alistair Siebert; Daniel K. Clare; Andrew Howe; Julika Radecke; Yun Song; Alain R. Townsend; Kuan Ying A. Huang; Elizabeth E. Fry; Juthathip Mongkolsapaya; Michael S. Diamond; Jingshan Ren; David I. Stuart; Gavin R. Screaton

doi:10.1016/j.cell.2021.02.032

The antigenic anatomy of SARS-CoV-2 receptor binding domain

Wanwisa Dejnirattisai, Daming Zhou, Helen M. Ginn, Helen M.E. Duyvesteyn, Piyada Supasa, James Brett Case, Yuguang Zhao, Thomas S. Walter, Alexander J. Mentzer, Chang Liu, Beibei Wang, Guido C. Paesen, Jose Slon-Campos, César López-Camacho, Natasha M. Kafai, Adam L. Bailey, Rita E. Chen, Baoling Ying, Craig Thompson, Jai BoltonAlex Fyfe, Sunetra Gupta, Tiong Kit Tan, Javier Gilbert-Jaramillo, William James, Michael Knight, Miles W. Carroll, Donal Skelly, Christina Dold, Yanchun Peng, Robert Levin, Tao Dong, Andrew J. Pollard, Julian C. Knight, Paul Klenerman, Nigel Temperton, David R. Hall, Mark A. Williams, Neil G. Paterson, Felicity K.R. Bertram, C. Alistair Siebert, Daniel K. Clare, Andrew Howe, Julika Radecke, Yun Song, Alain R. Townsend, Kuan Ying A. Huang, Elizabeth E. Fry, Juthathip Mongkolsapaya^*, Michael S. Diamond^*, Jingshan Ren^*, David I. Stuart^*, Gavin R. Screaton^*

^*Corresponding author for this work

School of Medicine

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

250 Scopus citations

Abstract

Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC₅₀ < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

Original language	English
Pages (from-to)	2183-2200.e22
Journal	Cell
Volume	184
Issue number	8
DOIs	https://doi.org/10.1016/j.cell.2021.02.032
State	Published - 15 04 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors

Keywords

coronavirus, SARS-CoV-2, anti-RBD antibody, receptor binding domain, antibody, immune responses, virus structure

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10.1016/j.cell.2021.02.032

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Dejnirattisai, W., Zhou, D., Ginn, H. M., Duyvesteyn, H. M. E., Supasa, P., Case, J. B., Zhao, Y., Walter, T. S., Mentzer, A. J., Liu, C., Wang, B., Paesen, G. C., Slon-Campos, J., López-Camacho, C., Kafai, N. M., Bailey, A. L., Chen, R. E., Ying, B., Thompson, C., ... Screaton, G. R. (2021). The antigenic anatomy of SARS-CoV-2 receptor binding domain. Cell, 184(8), 2183-2200.e22. https://doi.org/10.1016/j.cell.2021.02.032

@article{0c550ff589124fc182ab0892e969c7a0,

title = "The antigenic anatomy of SARS-CoV-2 receptor binding domain",

abstract = "Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.",

keywords = "coronavirus, SARS-CoV-2, anti-RBD antibody, receptor binding domain, antibody, immune responses, virus structure",

author = "Wanwisa Dejnirattisai and Daming Zhou and Ginn, {Helen M.} and Duyvesteyn, {Helen M.E.} and Piyada Supasa and Case, {James Brett} and Yuguang Zhao and Walter, {Thomas S.} and Mentzer, {Alexander J.} and Chang Liu and Beibei Wang and Paesen, {Guido C.} and Jose Slon-Campos and C{\'e}sar L{\'o}pez-Camacho and Kafai, {Natasha M.} and Bailey, {Adam L.} and Chen, {Rita E.} and Baoling Ying and Craig Thompson and Jai Bolton and Alex Fyfe and Sunetra Gupta and Tan, {Tiong Kit} and Javier Gilbert-Jaramillo and William James and Michael Knight and Carroll, {Miles W.} and Donal Skelly and Christina Dold and Yanchun Peng and Robert Levin and Tao Dong and Pollard, {Andrew J.} and Knight, {Julian C.} and Paul Klenerman and Nigel Temperton and Hall, {David R.} and Williams, {Mark A.} and Paterson, {Neil G.} and Bertram, {Felicity K.R.} and Siebert, {C. Alistair} and Clare, {Daniel K.} and Andrew Howe and Julika Radecke and Yun Song and Townsend, {Alain R.} and Huang, {Kuan Ying A.} and Fry, {Elizabeth E.} and Juthathip Mongkolsapaya and Diamond, {Michael S.} and Jingshan Ren and Stuart, {David I.} and Screaton, {Gavin R.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = apr,

day = "15",

doi = "10.1016/j.cell.2021.02.032",

language = "英语",

volume = "184",

pages = "2183--2200.e22",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "8",

}

Dejnirattisai, W, Zhou, D, Ginn, HM, Duyvesteyn, HME, Supasa, P, Case, JB, Zhao, Y, Walter, TS, Mentzer, AJ, Liu, C, Wang, B, Paesen, GC, Slon-Campos, J, López-Camacho, C, Kafai, NM, Bailey, AL, Chen, RE, Ying, B, Thompson, C, Bolton, J, Fyfe, A, Gupta, S, Tan, TK, Gilbert-Jaramillo, J, James, W, Knight, M, Carroll, MW, Skelly, D, Dold, C, Peng, Y, Levin, R, Dong, T, Pollard, AJ, Knight, JC, Klenerman, P, Temperton, N, Hall, DR, Williams, MA, Paterson, NG, Bertram, FKR, Siebert, CA, Clare, DK, Howe, A, Radecke, J, Song, Y, Townsend, AR, Huang, KYA, Fry, EE, Mongkolsapaya, J, Diamond, MS, Ren, J, Stuart, DI & Screaton, GR 2021, 'The antigenic anatomy of SARS-CoV-2 receptor binding domain', Cell, vol. 184, no. 8, pp. 2183-2200.e22. https://doi.org/10.1016/j.cell.2021.02.032

TY - JOUR

T1 - The antigenic anatomy of SARS-CoV-2 receptor binding domain

AU - Dejnirattisai, Wanwisa

AU - Zhou, Daming

AU - Ginn, Helen M.

AU - Duyvesteyn, Helen M.E.

AU - Supasa, Piyada

AU - Case, James Brett

AU - Zhao, Yuguang

AU - Walter, Thomas S.

AU - Mentzer, Alexander J.

AU - Liu, Chang

AU - Wang, Beibei

AU - Paesen, Guido C.

AU - Slon-Campos, Jose

AU - López-Camacho, César

AU - Kafai, Natasha M.

AU - Bailey, Adam L.

AU - Chen, Rita E.

AU - Ying, Baoling

AU - Thompson, Craig

AU - Bolton, Jai

AU - Fyfe, Alex

AU - Gupta, Sunetra

AU - Tan, Tiong Kit

AU - Gilbert-Jaramillo, Javier

AU - James, William

AU - Knight, Michael

AU - Carroll, Miles W.

AU - Skelly, Donal

AU - Dold, Christina

AU - Peng, Yanchun

AU - Levin, Robert

AU - Dong, Tao

AU - Pollard, Andrew J.

AU - Knight, Julian C.

AU - Klenerman, Paul

AU - Temperton, Nigel

AU - Hall, David R.

AU - Williams, Mark A.

AU - Paterson, Neil G.

AU - Bertram, Felicity K.R.

AU - Siebert, C. Alistair

AU - Clare, Daniel K.

AU - Howe, Andrew

AU - Radecke, Julika

AU - Song, Yun

AU - Townsend, Alain R.

AU - Huang, Kuan Ying A.

AU - Fry, Elizabeth E.

AU - Mongkolsapaya, Juthathip

AU - Diamond, Michael S.

AU - Ren, Jingshan

AU - Stuart, David I.

AU - Screaton, Gavin R.

PY - 2021/4/15

Y1 - 2021/4/15

N2 - Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

AB - Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

KW - coronavirus, SARS-CoV-2, anti-RBD antibody, receptor binding domain, antibody, immune responses, virus structure

UR - http://www.scopus.com/inward/record.url?scp=85102643098&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2021.02.032

DO - 10.1016/j.cell.2021.02.032

M3 - 文章

C2 - 33756110

AN - SCOPUS:85102643098

SN - 0092-8674

VL - 184

SP - 2183-2200.e22

JO - Cell

JF - Cell

IS - 8

ER -

The antigenic anatomy of SARS-CoV-2 receptor binding domain

Abstract

Bibliographical note

Keywords

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