Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

Thomas F. Rogers; Fangzhu Zhao; Deli Huang; Nathan Beutler; Alison Burns; Wan Ting He; Oliver Limbo; Chloe Smith; Ge Song; Jordan Woehl; Linlin Yang; Robert K. Abbott; Sean Callaghan; Elijah Garcia; Jonathan Hurtado; Mara Parren; Linghang Peng; Sydney Ramirez; James Ricketts; Michael J. Ricciardi; Stephen A. Rawlings; Nicholas C. Wu; Meng Yuan; Davey M. Smith; David Nemazee; John R. Teijaro; James E. Voss; Ian A. Wilson; Raiees Andrabi; Bryan Briney; Elise Landais; Devin Sok; Joseph G. Jardine; Dennis R. Burton

doi:10.1126/science.abc7520

Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

Thomas F. Rogers, Fangzhu Zhao, Deli Huang, Nathan Beutler, Alison Burns, Wan Ting He, Oliver Limbo, Chloe Smith, Ge Song, Jordan Woehl, Linlin Yang, Robert K. Abbott, Sean Callaghan, Elijah Garcia, Jonathan Hurtado, Mara Parren, Linghang Peng, Sydney Ramirez, James Ricketts, Michael J. RicciardiStephen A. Rawlings, Nicholas C. Wu, Meng Yuan, Davey M. Smith, David Nemazee, John R. Teijaro, James E. Voss, Ian A. Wilson, Raiees Andrabi, Bryan Briney, Elise Landais, Devin Sok, Joseph G. Jardine, Dennis R. Burton

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Abstract

Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.

Original language	English (US)
Pages (from-to)	956-963
Number of pages	8
Journal	Science
Volume	369
Issue number	6506
DOIs	https://doi.org/10.1126/science.abc7520
State	Published - Aug 21 2020
Externally published	Yes

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Rogers, T. F., Zhao, F., Huang, D., Beutler, N., Burns, A., He, W. T., Limbo, O., Smith, C., Song, G., Woehl, J., Yang, L., Abbott, R. K., Callaghan, S., Garcia, E., Hurtado, J., Parren, M., Peng, L., Ramirez, S., Ricketts, J., ... Burton, D. R. (2020). Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science, 369(6506), 956-963. https://doi.org/10.1126/science.abc7520

Rogers, TF, Zhao, F, Huang, D, Beutler, N, Burns, A, He, WT, Limbo, O, Smith, C, Song, G, Woehl, J, Yang, L, Abbott, RK, Callaghan, S, Garcia, E, Hurtado, J, Parren, M, Peng, L, Ramirez, S, Ricketts, J, Ricciardi, MJ, Rawlings, SA, Wu, NC, Yuan, M, Smith, DM, Nemazee, D, Teijaro, JR, Voss, JE, Wilson, IA, Andrabi, R, Briney, B, Landais, E, Sok, D, Jardine, JG & Burton, DR 2020, 'Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model', Science, vol. 369, no. 6506, pp. 956-963. https://doi.org/10.1126/science.abc7520

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title = "Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model",

abstract = "Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.",

author = "Rogers, {Thomas F.} and Fangzhu Zhao and Deli Huang and Nathan Beutler and Alison Burns and He, {Wan Ting} and Oliver Limbo and Chloe Smith and Ge Song and Jordan Woehl and Linlin Yang and Abbott, {Robert K.} and Sean Callaghan and Elijah Garcia and Jonathan Hurtado and Mara Parren and Linghang Peng and Sydney Ramirez and James Ricketts and Ricciardi, {Michael J.} and Rawlings, {Stephen A.} and Wu, {Nicholas C.} and Meng Yuan and Smith, {Davey M.} and David Nemazee and Teijaro, {John R.} and Voss, {James E.} and Wilson, {Ian A.} and Raiees Andrabi and Bryan Briney and Elise Landais and Devin Sok and Jardine, {Joseph G.} and Burton, {Dennis R.}",

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doi = "10.1126/science.abc7520",

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AU - Burns, Alison

AU - He, Wan Ting

AU - Limbo, Oliver

AU - Smith, Chloe

AU - Song, Ge

AU - Woehl, Jordan

AU - Yang, Linlin

AU - Abbott, Robert K.

AU - Callaghan, Sean

AU - Garcia, Elijah

AU - Hurtado, Jonathan

AU - Parren, Mara

AU - Peng, Linghang

AU - Ramirez, Sydney

AU - Ricketts, James

AU - Ricciardi, Michael J.

AU - Rawlings, Stephen A.

AU - Wu, Nicholas C.

AU - Yuan, Meng

AU - Smith, Davey M.

AU - Nemazee, David

AU - Teijaro, John R.

AU - Voss, James E.

AU - Wilson, Ian A.

AU - Andrabi, Raiees

AU - Briney, Bryan

AU - Landais, Elise

AU - Sok, Devin

AU - Jardine, Joseph G.

AU - Burton, Dennis R.

PY - 2020/8/21

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Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

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