Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses

Bailey B. Banach; Gabriele Cerutti; Ahmed S. Fahad; Chen Hsiang Shen; Matheus Oliveira De Souza; Phinikoula S. Katsamba; Yaroslav Tsybovsky; Pengfei Wang; Manoj S. Nair; Yaoxing Huang; Irene M. Francino-Urdániz; Paul J. Steiner; Matías Gutiérrez-González; Lihong Liu; Sheila N. López Acevedo; Alexandra F. Nazzari; Jacy R. Wolfe; Yang Luo; Adam S. Olia; I. Ting Teng; Jian Yu; Tongqing Zhou; Eswar R. Reddem; Jude Bimela; Xiaoli Pan; Bharat Madan; Amy D. Laflin; Rajani Nimrania; Kwok Yung Yuen; Timothy A. Whitehead; David D. Ho; Peter D. Kwong; Lawrence Shapiro; Brandon J. DeKosky

doi:10.1016/j.celrep.2021.109771

Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses

Bailey B. Banach, Gabriele Cerutti, Ahmed S. Fahad, Chen Hsiang Shen, Matheus Oliveira De Souza, Phinikoula S. Katsamba, Yaroslav Tsybovsky, Pengfei Wang, Manoj S. Nair, Yaoxing Huang, Irene M. Francino-Urdániz, Paul J. Steiner, Matías Gutiérrez-González, Lihong Liu, Sheila N. López Acevedo, Alexandra F. Nazzari, Jacy R. Wolfe, Yang Luo, Adam S. Olia, I. Ting TengJian Yu, Tongqing Zhou, Eswar R. Reddem, Jude Bimela, Xiaoli Pan, Bharat Madan, Amy D. Laflin, Rajani Nimrania, Kwok Yung Yuen, Timothy A. Whitehead, David D. Ho, Peter D. Kwong, Lawrence Shapiro, Brandon J. DeKosky

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

30 Citations (Scopus)

Abstract

Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be ∼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.

Original language	English
Article number	109771
Journal	Cell Reports
Volume	37
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2021.109771
Publication status	Published - Oct 5 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 The Author(s)

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology

Keywords

B-cell
SARS-CoV-2
biotechnology
immunity
neutralization
public antibody
virology
yeast display

Access to Document

10.1016/j.celrep.2021.109771

Cite this

Banach, B. B., Cerutti, G., Fahad, A. S., Shen, C. H., Oliveira De Souza, M., Katsamba, P. S., Tsybovsky, Y., Wang, P., Nair, M. S., Huang, Y., Francino-Urdániz, I. M., Steiner, P. J., Gutiérrez-González, M., Liu, L., López Acevedo, S. N., Nazzari, A. F., Wolfe, J. R., Luo, Y., Olia, A. S., ... DeKosky, B. J. (2021). Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses. Cell Reports, 37(1), Article 109771. https://doi.org/10.1016/j.celrep.2021.109771

Banach, BB, Cerutti, G, Fahad, AS, Shen, CH, Oliveira De Souza, M, Katsamba, PS, Tsybovsky, Y, Wang, P, Nair, MS, Huang, Y, Francino-Urdániz, IM, Steiner, PJ, Gutiérrez-González, M, Liu, L, López Acevedo, SN, Nazzari, AF, Wolfe, JR, Luo, Y, Olia, AS, Teng, IT, Yu, J, Zhou, T, Reddem, ER, Bimela, J, Pan, X, Madan, B, Laflin, AD, Nimrania, R, Yuen, KY, Whitehead, TA, Ho, DD, Kwong, PD, Shapiro, L & DeKosky, BJ 2021, 'Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses', Cell Reports, vol. 37, no. 1, 109771. https://doi.org/10.1016/j.celrep.2021.109771

@article{fc892d715e96452ca228c6a617a23d8f,

title = "Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses",

abstract = "Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be ∼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.",

keywords = "B-cell, SARS-CoV-2, biotechnology, immunity, neutralization, public antibody, virology, yeast display",

author = "Banach, {Bailey B.} and Gabriele Cerutti and Fahad, {Ahmed S.} and Shen, {Chen Hsiang} and {Oliveira De Souza}, Matheus and Katsamba, {Phinikoula S.} and Yaroslav Tsybovsky and Pengfei Wang and Nair, {Manoj S.} and Yaoxing Huang and Francino-Urd{\'a}niz, {Irene M.} and Steiner, {Paul J.} and Mat{\'i}as Guti{\'e}rrez-Gonz{\'a}lez and Lihong Liu and {L{\'o}pez Acevedo}, {Sheila N.} and Nazzari, {Alexandra F.} and Wolfe, {Jacy R.} and Yang Luo and Olia, {Adam S.} and Teng, {I. Ting} and Jian Yu and Tongqing Zhou and Reddem, {Eswar R.} and Jude Bimela and Xiaoli Pan and Bharat Madan and Laflin, {Amy D.} and Rajani Nimrania and Yuen, {Kwok Yung} and Whitehead, {Timothy A.} and Ho, {David D.} and Kwong, {Peter D.} and Lawrence Shapiro and DeKosky, {Brandon J.}",

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

year = "2021",

month = oct,

day = "5",

doi = "10.1016/j.celrep.2021.109771",

language = "English",

volume = "37",

journal = "Cell Reports",

issn = "2211-1247",

number = "1",

}

TY - JOUR

T1 - Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses

AU - Banach, Bailey B.

AU - Cerutti, Gabriele

AU - Fahad, Ahmed S.

AU - Shen, Chen Hsiang

AU - Oliveira De Souza, Matheus

AU - Katsamba, Phinikoula S.

AU - Tsybovsky, Yaroslav

AU - Wang, Pengfei

AU - Nair, Manoj S.

AU - Huang, Yaoxing

AU - Francino-Urdániz, Irene M.

AU - Steiner, Paul J.

AU - Gutiérrez-González, Matías

AU - Liu, Lihong

AU - López Acevedo, Sheila N.

AU - Nazzari, Alexandra F.

AU - Wolfe, Jacy R.

AU - Luo, Yang

AU - Olia, Adam S.

AU - Teng, I. Ting

AU - Yu, Jian

AU - Zhou, Tongqing

AU - Reddem, Eswar R.

AU - Bimela, Jude

AU - Pan, Xiaoli

AU - Madan, Bharat

AU - Laflin, Amy D.

AU - Nimrania, Rajani

AU - Yuen, Kwok Yung

AU - Whitehead, Timothy A.

AU - Ho, David D.

AU - Kwong, Peter D.

AU - Shapiro, Lawrence

AU - DeKosky, Brandon J.

PY - 2021/10/5

Y1 - 2021/10/5

N2 - Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be ∼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.

AB - Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be ∼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.

KW - B-cell

KW - SARS-CoV-2

KW - biotechnology

KW - immunity

KW - neutralization

KW - public antibody

KW - virology

KW - yeast display

UR - http://www.scopus.com/inward/record.url?scp=85115986353&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85115986353&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.109771

DO - 10.1016/j.celrep.2021.109771

M3 - Article

C2 - 34587480

AN - SCOPUS:85115986353

SN - 2211-1247

VL - 37

JO - Cell Reports

JF - Cell Reports

IS - 1

M1 - 109771

ER -

Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Keywords

Access to Document

Other files and links

Cite this