The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

Chang Liu; Daming Zhou; Rungtiwa Nutalai; Helen M.E. Duyvesteyn; Aekkachai Tuekprakhon; Helen M. Ginn; Wanwisa Dejnirattisai; Piyada Supasa; Alexander J. Mentzer; Beibei Wang; James Brett Case; Yuguang Zhao; Donal T. Skelly; Rita E. Chen; Sile Ann Johnson; Thomas G. Ritter; Chris Mason; Tariq Malik; Nigel Temperton; Neil G. Paterson; Mark A. Williams; David R. Hall; Daniel K. Clare; Andrew Howe; Philip J.R. Goulder; Elizabeth E. Fry; Michael S. Diamond; Juthathip Mongkolsapaya; Jingshan Ren; David I. Stuart; Gavin R. Screaton

doi:10.1016/j.chom.2021.11.013

The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

Chang Liu, Daming Zhou, Rungtiwa Nutalai, Helen M.E. Duyvesteyn, Aekkachai Tuekprakhon, Helen M. Ginn, Wanwisa Dejnirattisai, Piyada Supasa, Alexander J. Mentzer, Beibei Wang, James Brett Case, Yuguang Zhao, Donal T. Skelly, Rita E. Chen, Sile Ann Johnson, Thomas G. Ritter, Chris Mason, Tariq Malik, Nigel Temperton, Neil G. PatersonMark A. Williams, David R. Hall, Daniel K. Clare, Andrew Howe, Philip J.R. Goulder, Elizabeth E. Fry, Michael S. Diamond, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin R. Screaton

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53 Scopus citations

Abstract

Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.

Original language	English
Pages (from-to)	53-68.e12
Journal	Cell Host and Microbe
Volume	30
Issue number	1
DOIs	https://doi.org/10.1016/j.chom.2021.11.013
State	Published - Jan 12 2022

Keywords

Beta variant
COVID-19
SARS-CoV-2
antibody
immune responses
neutralization
receptor-binding domain
spike protein
structure
vaccine

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10.1016/j.chom.2021.11.013

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Liu, C., Zhou, D., Nutalai, R., Duyvesteyn, H. M. E., Tuekprakhon, A., Ginn, H. M., Dejnirattisai, W., Supasa, P., Mentzer, A. J., Wang, B., Case, J. B., Zhao, Y., Skelly, D. T., Chen, R. E., Johnson, S. A., Ritter, T. G., Mason, C., Malik, T., Temperton, N., ... Screaton, G. R. (2022). The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants. Cell Host and Microbe, 30(1), 53-68.e12. https://doi.org/10.1016/j.chom.2021.11.013

@article{dc58ecc067c34110a71f1db593f4e140,

title = "The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants",

abstract = "Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.",

keywords = "Beta variant, COVID-19, SARS-CoV-2, antibody, immune responses, neutralization, receptor-binding domain, spike protein, structure, vaccine",

author = "Chang Liu and Daming Zhou and Rungtiwa Nutalai and Duyvesteyn, {Helen M.E.} and Aekkachai Tuekprakhon and Ginn, {Helen M.} and Wanwisa Dejnirattisai and Piyada Supasa and Mentzer, {Alexander J.} and Beibei Wang and Case, {James Brett} and Yuguang Zhao and Skelly, {Donal T.} and Chen, {Rita E.} and Johnson, {Sile Ann} and Ritter, {Thomas G.} and Chris Mason and Tariq Malik and Nigel Temperton and Paterson, {Neil G.} and Williams, {Mark A.} and Hall, {David R.} and Clare, {Daniel K.} and Andrew Howe and Goulder, {Philip J.R.} and Fry, {Elizabeth E.} and Diamond, {Michael S.} and Juthathip Mongkolsapaya and Jingshan Ren and Stuart, {David I.} and Screaton, {Gavin R.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2022",

month = jan,

day = "12",

doi = "10.1016/j.chom.2021.11.013",

language = "English",

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Liu, C, Zhou, D, Nutalai, R, Duyvesteyn, HME, Tuekprakhon, A, Ginn, HM, Dejnirattisai, W, Supasa, P, Mentzer, AJ, Wang, B, Case, JB, Zhao, Y, Skelly, DT, Chen, RE, Johnson, SA, Ritter, TG, Mason, C, Malik, T, Temperton, N, Paterson, NG, Williams, MA, Hall, DR, Clare, DK, Howe, A, Goulder, PJR, Fry, EE, Diamond, MS, Mongkolsapaya, J, Ren, J, Stuart, DI & Screaton, GR 2022, 'The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants', Cell Host and Microbe, vol. 30, no. 1, pp. 53-68.e12. https://doi.org/10.1016/j.chom.2021.11.013

TY - JOUR

T1 - The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

AU - Liu, Chang

AU - Zhou, Daming

AU - Nutalai, Rungtiwa

AU - Duyvesteyn, Helen M.E.

AU - Tuekprakhon, Aekkachai

AU - Ginn, Helen M.

AU - Dejnirattisai, Wanwisa

AU - Supasa, Piyada

AU - Mentzer, Alexander J.

AU - Wang, Beibei

AU - Case, James Brett

AU - Zhao, Yuguang

AU - Skelly, Donal T.

AU - Chen, Rita E.

AU - Johnson, Sile Ann

AU - Ritter, Thomas G.

AU - Mason, Chris

AU - Malik, Tariq

AU - Temperton, Nigel

AU - Paterson, Neil G.

AU - Williams, Mark A.

AU - Hall, David R.

AU - Clare, Daniel K.

AU - Howe, Andrew

AU - Goulder, Philip J.R.

AU - Fry, Elizabeth E.

AU - Diamond, Michael S.

AU - Mongkolsapaya, Juthathip

AU - Ren, Jingshan

AU - Stuart, David I.

AU - Screaton, Gavin R.

PY - 2022/1/12

Y1 - 2022/1/12

N2 - Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.

AB - Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.

KW - Beta variant

KW - COVID-19

KW - SARS-CoV-2

KW - antibody

KW - immune responses

KW - neutralization

KW - receptor-binding domain

KW - spike protein

KW - structure

KW - vaccine

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U2 - 10.1016/j.chom.2021.11.013

DO - 10.1016/j.chom.2021.11.013

M3 - Article

C2 - 34921776

AN - SCOPUS:85121345277

SN - 1931-3128

VL - 30

SP - 53-68.e12

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 1

ER -

The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

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