Discovery and characterization of a pan-betacoronavirus S2-binding antibody

Nicole V. Johnson; Steven C. Wall; Kevin J. Kramer; Clinton M. Holt; Sivakumar Periasamy; Simone I. Richardson; Nelia P. Manamela; Naveenchandra Suryadevara; Emanuele Andreano; Ida Paciello; Giulio Pierleoni; Giulia Piccini; Ying Huang; Pan Ge; James D. Allen; Naoko Uno; Andrea R. Shiakolas; Kelsey A. Pilewski; Rachel S. Nargi; Rachel E. Sutton; Alexandria A. Abu-Shmais; Robert Parks; Barton F. Haynes; Robert H. Carnahan; James E. Crowe; Emanuele Montomoli; Rino Rappuoli; Alexander Bukreyev; Ted M. Ross; Giuseppe A. Sautto; Jason S. McLellan; Ivelin S. Georgiev

doi:10.1016/j.str.2024.08.022

Discovery and characterization of a pan-betacoronavirus S2-binding antibody

Nicole V. Johnson, Steven C. Wall, Kevin J. Kramer, Clinton M. Holt, Sivakumar Periasamy, Simone I. Richardson, Nelia P. Manamela, Naveenchandra Suryadevara, Emanuele Andreano, Ida Paciello, Giulio Pierleoni, Giulia Piccini, Ying Huang, Pan Ge, James D. Allen, Naoko Uno, Andrea R. Shiakolas, Kelsey A. Pilewski, Rachel S. Nargi, Rachel E. SuttonAlexandria A. Abu-Shmais, Robert Parks, Barton F. Haynes, Robert H. Carnahan, James E. Crowe, Emanuele Montomoli, Rino Rappuoli, Alexander Bukreyev, Ted M. Ross, Giuseppe A. Sautto, Jason S. McLellan, Ivelin S. Georgiev

Pathology

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

5 Scopus citations

Abstract

The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.

Original language	English (US)
Pages (from-to)	1893-1909.e11
Journal	Structure
Volume	32
Issue number	11
DOIs	https://doi.org/10.1016/j.str.2024.08.022
State	Published - Nov 7 2024

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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10.1016/j.str.2024.08.022

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Johnson, N. V., Wall, S. C., Kramer, K. J., Holt, C. M., Periasamy, S., Richardson, S. I., Manamela, N. P., Suryadevara, N., Andreano, E., Paciello, I., Pierleoni, G., Piccini, G., Huang, Y., Ge, P., Allen, J. D., Uno, N., Shiakolas, A. R., Pilewski, K. A., Nargi, R. S., ... Georgiev, I. S. (2024). Discovery and characterization of a pan-betacoronavirus S2-binding antibody. Structure, 32(11), 1893-1909.e11. https://doi.org/10.1016/j.str.2024.08.022

Johnson, NV, Wall, SC, Kramer, KJ, Holt, CM, Periasamy, S, Richardson, SI, Manamela, NP, Suryadevara, N, Andreano, E, Paciello, I, Pierleoni, G, Piccini, G, Huang, Y, Ge, P, Allen, JD, Uno, N, Shiakolas, AR, Pilewski, KA, Nargi, RS, Sutton, RE, Abu-Shmais, AA, Parks, R, Haynes, BF, Carnahan, RH, Crowe, JE, Montomoli, E, Rappuoli, R, Bukreyev, A, Ross, TM, Sautto, GA, McLellan, JS & Georgiev, IS 2024, 'Discovery and characterization of a pan-betacoronavirus S2-binding antibody', Structure, vol. 32, no. 11, pp. 1893-1909.e11. https://doi.org/10.1016/j.str.2024.08.022

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title = "Discovery and characterization of a pan-betacoronavirus S2-binding antibody",

abstract = "The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.",

author = "Johnson, {Nicole V.} and Wall, {Steven C.} and Kramer, {Kevin J.} and Holt, {Clinton M.} and Sivakumar Periasamy and Richardson, {Simone I.} and Manamela, {Nelia P.} and Naveenchandra Suryadevara and Emanuele Andreano and Ida Paciello and Giulio Pierleoni and Giulia Piccini and Ying Huang and Pan Ge and Allen, {James D.} and Naoko Uno and Shiakolas, {Andrea R.} and Pilewski, {Kelsey A.} and Nargi, {Rachel S.} and Sutton, {Rachel E.} and Abu-Shmais, {Alexandria A.} and Robert Parks and Haynes, {Barton F.} and Carnahan, {Robert H.} and Crowe, {James E.} and Emanuele Montomoli and Rino Rappuoli and Alexander Bukreyev and Ross, {Ted M.} and Sautto, {Giuseppe A.} and McLellan, {Jason S.} and Georgiev, {Ivelin S.}",

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AU - Johnson, Nicole V.

AU - Wall, Steven C.

AU - Kramer, Kevin J.

AU - Holt, Clinton M.

AU - Periasamy, Sivakumar

AU - Richardson, Simone I.

AU - Manamela, Nelia P.

AU - Suryadevara, Naveenchandra

AU - Andreano, Emanuele

AU - Paciello, Ida

AU - Pierleoni, Giulio

AU - Piccini, Giulia

AU - Huang, Ying

AU - Ge, Pan

AU - Allen, James D.

AU - Uno, Naoko

AU - Shiakolas, Andrea R.

AU - Pilewski, Kelsey A.

AU - Nargi, Rachel S.

AU - Sutton, Rachel E.

AU - Abu-Shmais, Alexandria A.

AU - Parks, Robert

AU - Haynes, Barton F.

AU - Carnahan, Robert H.

AU - Crowe, James E.

AU - Montomoli, Emanuele

AU - Rappuoli, Rino

AU - Bukreyev, Alexander

AU - Ross, Ted M.

AU - Sautto, Giuseppe A.

AU - McLellan, Jason S.

AU - Georgiev, Ivelin S.

PY - 2024/11/7

Y1 - 2024/11/7

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AB - The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.

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Discovery and characterization of a pan-betacoronavirus S2-binding antibody

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