Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions

Andrea R. Shiakolas; Kevin J. Kramer; Daniel Wrapp; Simone I. Richardson; Alexandra Schäfer; Steven Wall; Nianshuang Wang; Katarzyna Janowska; Kelsey A. Pilewski; Rohit Venkat; Robert Parks; Nelia P. Manamela; Nagarajan Raju; Emilee Friedman Fechter; Clinton M. Holt; Naveenchandra Suryadevara; Rita E. Chen; David R. Martinez; Rachel S. Nargi; Rachel E. Sutton; Julie E. Ledgerwood; Barney S. Graham; Michael S. Diamond; Barton F. Haynes; Priyamvada Acharya; Robert H. Carnahan; James E. Crowe; Ralph S. Baric; Lynn Morris; Jason S. McLellan; Ivelin S. Georgiev

doi:10.1016/j.xcrm.2021.100313

Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions

Andrea R. Shiakolas, Kevin J. Kramer, Daniel Wrapp, Simone I. Richardson, Alexandra Schäfer, Steven Wall, Nianshuang Wang, Katarzyna Janowska, Kelsey A. Pilewski, Rohit Venkat, Robert Parks, Nelia P. Manamela, Nagarajan Raju, Emilee Friedman Fechter, Clinton M. Holt, Naveenchandra Suryadevara, Rita E. Chen, David R. Martinez, Rachel S. Nargi, Rachel E. SuttonJulie E. Ledgerwood, Barney S. Graham, Michael S. Diamond, Barton F. Haynes, Priyamvada Acharya, Robert H. Carnahan, James E. Crowe, Ralph S. Baric, Lynn Morris, Jason S. McLellan, Ivelin S. Georgiev

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53 Scopus citations

Abstract

The continual emergence of novel coronaviruses (CoV), such as severe acute respiratory syndrome-(SARS)-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. From a recovered SARS-CoV donor sample, we identify and characterize a panel of six monoclonal antibodies that cross-react with CoV spike (S) proteins from the highly pathogenic SARS-CoV and SARS-CoV-2, and demonstrate a spectrum of reactivity against other CoVs. Epitope mapping reveals that these antibodies recognize multiple epitopes on SARS-CoV-2 S, including the receptor-binding domain, the N-terminal domain, and the S2 subunit. Functional characterization demonstrates that the antibodies mediate phagocytosis—and in some cases trogocytosis—but not neutralization in vitro. When tested in vivo in murine models, two of the antibodies demonstrate a reduction in hemorrhagic pathology in the lungs. The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies.

Original language	English
Article number	100313
Journal	Cell Reports Medicine
Volume	2
Issue number	6
DOIs	https://doi.org/10.1016/j.xcrm.2021.100313
State	Published - Jun 15 2021

Keywords

COVID-19
Fc effector function
LIBRA-seq
SARS-CoV-2
antibody discovery
cross-reactivity
single-cell sequencing

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10.1016/j.xcrm.2021.100313

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Shiakolas, A. R., Kramer, K. J., Wrapp, D., Richardson, S. I., Schäfer, A., Wall, S., Wang, N., Janowska, K., Pilewski, K. A., Venkat, R., Parks, R., Manamela, N. P., Raju, N., Fechter, E. F., Holt, C. M., Suryadevara, N., Chen, R. E., Martinez, D. R., Nargi, R. S., ... Georgiev, I. S. (2021). Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions. Cell Reports Medicine, 2(6), Article 100313. https://doi.org/10.1016/j.xcrm.2021.100313

@article{7cd0a78efac044389d2b18cc620c871e,

title = "Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions",

abstract = "The continual emergence of novel coronaviruses (CoV), such as severe acute respiratory syndrome-(SARS)-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. From a recovered SARS-CoV donor sample, we identify and characterize a panel of six monoclonal antibodies that cross-react with CoV spike (S) proteins from the highly pathogenic SARS-CoV and SARS-CoV-2, and demonstrate a spectrum of reactivity against other CoVs. Epitope mapping reveals that these antibodies recognize multiple epitopes on SARS-CoV-2 S, including the receptor-binding domain, the N-terminal domain, and the S2 subunit. Functional characterization demonstrates that the antibodies mediate phagocytosis—and in some cases trogocytosis—but not neutralization in vitro. When tested in vivo in murine models, two of the antibodies demonstrate a reduction in hemorrhagic pathology in the lungs. The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies.",

keywords = "COVID-19, Fc effector function, LIBRA-seq, SARS-CoV-2, antibody discovery, cross-reactivity, single-cell sequencing",

author = "Shiakolas, {Andrea R.} and Kramer, {Kevin J.} and Daniel Wrapp and Richardson, {Simone I.} and Alexandra Sch{\"a}fer and Steven Wall and Nianshuang Wang and Katarzyna Janowska and Pilewski, {Kelsey A.} and Rohit Venkat and Robert Parks and Manamela, {Nelia P.} and Nagarajan Raju and Fechter, {Emilee Friedman} and Holt, {Clinton M.} and Naveenchandra Suryadevara and Chen, {Rita E.} and Martinez, {David R.} and Nargi, {Rachel S.} and Sutton, {Rachel E.} and Ledgerwood, {Julie E.} and Graham, {Barney S.} and Diamond, {Michael S.} and Haynes, {Barton F.} and Priyamvada Acharya and Carnahan, {Robert H.} and Crowe, {James E.} and Baric, {Ralph S.} and Lynn Morris and McLellan, {Jason S.} and Georgiev, {Ivelin S.}",

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

year = "2021",

month = jun,

day = "15",

doi = "10.1016/j.xcrm.2021.100313",

language = "English",

volume = "2",

journal = "Cell Reports Medicine",

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Shiakolas, AR, Kramer, KJ, Wrapp, D, Richardson, SI, Schäfer, A, Wall, S, Wang, N, Janowska, K, Pilewski, KA, Venkat, R, Parks, R, Manamela, NP, Raju, N, Fechter, EF, Holt, CM, Suryadevara, N, Chen, RE, Martinez, DR, Nargi, RS, Sutton, RE, Ledgerwood, JE, Graham, BS, Diamond, MS, Haynes, BF, Acharya, P, Carnahan, RH, Crowe, JE, Baric, RS, Morris, L, McLellan, JS & Georgiev, IS 2021, 'Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions', Cell Reports Medicine, vol. 2, no. 6, 100313. https://doi.org/10.1016/j.xcrm.2021.100313

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T1 - Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions

AU - Shiakolas, Andrea R.

AU - Kramer, Kevin J.

AU - Wrapp, Daniel

AU - Richardson, Simone I.

AU - Schäfer, Alexandra

AU - Wall, Steven

AU - Wang, Nianshuang

AU - Janowska, Katarzyna

AU - Pilewski, Kelsey A.

AU - Venkat, Rohit

AU - Parks, Robert

AU - Manamela, Nelia P.

AU - Raju, Nagarajan

AU - Fechter, Emilee Friedman

AU - Holt, Clinton M.

AU - Suryadevara, Naveenchandra

AU - Chen, Rita E.

AU - Martinez, David R.

AU - Nargi, Rachel S.

AU - Sutton, Rachel E.

AU - Ledgerwood, Julie E.

AU - Graham, Barney S.

AU - Diamond, Michael S.

AU - Haynes, Barton F.

AU - Acharya, Priyamvada

AU - Carnahan, Robert H.

AU - Crowe, James E.

AU - Baric, Ralph S.

AU - Morris, Lynn

AU - McLellan, Jason S.

AU - Georgiev, Ivelin S.

PY - 2021/6/15

Y1 - 2021/6/15

N2 - The continual emergence of novel coronaviruses (CoV), such as severe acute respiratory syndrome-(SARS)-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. From a recovered SARS-CoV donor sample, we identify and characterize a panel of six monoclonal antibodies that cross-react with CoV spike (S) proteins from the highly pathogenic SARS-CoV and SARS-CoV-2, and demonstrate a spectrum of reactivity against other CoVs. Epitope mapping reveals that these antibodies recognize multiple epitopes on SARS-CoV-2 S, including the receptor-binding domain, the N-terminal domain, and the S2 subunit. Functional characterization demonstrates that the antibodies mediate phagocytosis—and in some cases trogocytosis—but not neutralization in vitro. When tested in vivo in murine models, two of the antibodies demonstrate a reduction in hemorrhagic pathology in the lungs. The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies.

AB - The continual emergence of novel coronaviruses (CoV), such as severe acute respiratory syndrome-(SARS)-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. From a recovered SARS-CoV donor sample, we identify and characterize a panel of six monoclonal antibodies that cross-react with CoV spike (S) proteins from the highly pathogenic SARS-CoV and SARS-CoV-2, and demonstrate a spectrum of reactivity against other CoVs. Epitope mapping reveals that these antibodies recognize multiple epitopes on SARS-CoV-2 S, including the receptor-binding domain, the N-terminal domain, and the S2 subunit. Functional characterization demonstrates that the antibodies mediate phagocytosis—and in some cases trogocytosis—but not neutralization in vitro. When tested in vivo in murine models, two of the antibodies demonstrate a reduction in hemorrhagic pathology in the lungs. The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies.

KW - COVID-19

KW - Fc effector function

KW - LIBRA-seq

KW - SARS-CoV-2

KW - antibody discovery

KW - cross-reactivity

KW - single-cell sequencing

UR - http://www.scopus.com/inward/record.url?scp=85107567133&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2021.100313

DO - 10.1016/j.xcrm.2021.100313

M3 - Article

C2 - 34056628

AN - SCOPUS:85107567133

SN - 2666-3791

VL - 2

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 6

M1 - 100313

ER -

Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions

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