A potently neutralizing antibody protects mice against SARS-CoV-2 infection

Wafaa B. Alsoussi; Jackson S. Turner; James B. Case; Haiyan Zhao; Aaron J. Schmitz; Julian Q. Zhou; Rita E. Chen; Tingting Lei; Amena A. Rizk; Katherine M. McIntire; Emma S. Winkler; Julie M. Fox; Natasha M. Kafai; Larissa B. Thackray; Ahmed O. Hassan; Fatima Amanat; Florian Krammer; Corey T. Watson; Steven H. Kleinstein; Daved H. Fremont; Michael S. Diamond; Ali H. Ellebedy

doi:10.4049/jimmunol.2000583

A potently neutralizing antibody protects mice against SARS-CoV-2 infection

Wafaa B. Alsoussi, Jackson S. Turner, James B. Case, Haiyan Zhao, Aaron J. Schmitz, Julian Q. Zhou, Rita E. Chen, Tingting Lei, Amena A. Rizk, Katherine M. McIntire, Emma S. Winkler, Julie M. Fox, Natasha M. Kafai, Larissa B. Thackray, Ahmed O. Hassan, Fatima Amanat, Florian Krammer, Corey T. Watson, Steven H. Kleinstein, Daved H. FremontMichael S. Diamond, Ali H. Ellebedy

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141 Scopus citations

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.

Original language	English
Pages (from-to)	915-922
Number of pages	8
Journal	Journal of Immunology
Volume	205
Issue number	4
DOIs	https://doi.org/10.4049/jimmunol.2000583
State	Published - Aug 15 2020

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Alsoussi, W. B., Turner, J. S., Case, J. B., Zhao, H., Schmitz, A. J., Zhou, J. Q., Chen, R. E., Lei, T., Rizk, A. A., McIntire, K. M., Winkler, E. S., Fox, J. M., Kafai, N. M., Thackray, L. B., Hassan, A. O., Amanat, F., Krammer, F., Watson, C. T., Kleinstein, S. H., ... Ellebedy, A. H. (2020). A potently neutralizing antibody protects mice against SARS-CoV-2 infection. Journal of Immunology, 205(4), 915-922. https://doi.org/10.4049/jimmunol.2000583

@article{0011c69fa20840939f5c0a51e4b54dca,

title = "A potently neutralizing antibody protects mice against SARS-CoV-2 infection",

abstract = "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.",

author = "Alsoussi, {Wafaa B.} and Turner, {Jackson S.} and Case, {James B.} and Haiyan Zhao and Schmitz, {Aaron J.} and Zhou, {Julian Q.} and Chen, {Rita E.} and Tingting Lei and Rizk, {Amena A.} and McIntire, {Katherine M.} and Winkler, {Emma S.} and Fox, {Julie M.} and Kafai, {Natasha M.} and Thackray, {Larissa B.} and Hassan, {Ahmed O.} and Fatima Amanat and Florian Krammer and Watson, {Corey T.} and Kleinstein, {Steven H.} and Fremont, {Daved H.} and Diamond, {Michael S.} and Ellebedy, {Ali H.}",

year = "2020",

month = aug,

day = "15",

doi = "10.4049/jimmunol.2000583",

language = "English",

volume = "205",

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journal = "Journal of Immunology",

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Alsoussi, WB, Turner, JS , Case, JB, Zhao, H, Schmitz, AJ, Zhou, JQ, Chen, RE, Lei, T, Rizk, AA, McIntire, KM, Winkler, ES, Fox, JM, Kafai, NM, Thackray, LB, Hassan, AO, Amanat, F, Krammer, F, Watson, CT, Kleinstein, SH, Fremont, DH , Diamond, MS & Ellebedy, AH 2020, 'A potently neutralizing antibody protects mice against SARS-CoV-2 infection', Journal of Immunology, vol. 205, no. 4, pp. 915-922. https://doi.org/10.4049/jimmunol.2000583

TY - JOUR

T1 - A potently neutralizing antibody protects mice against SARS-CoV-2 infection

AU - Alsoussi, Wafaa B.

AU - Turner, Jackson S.

AU - Case, James B.

AU - Zhao, Haiyan

AU - Schmitz, Aaron J.

AU - Zhou, Julian Q.

AU - Chen, Rita E.

AU - Lei, Tingting

AU - Rizk, Amena A.

AU - McIntire, Katherine M.

AU - Winkler, Emma S.

AU - Fox, Julie M.

AU - Kafai, Natasha M.

AU - Thackray, Larissa B.

AU - Hassan, Ahmed O.

AU - Amanat, Fatima

AU - Krammer, Florian

AU - Watson, Corey T.

AU - Kleinstein, Steven H.

AU - Fremont, Daved H.

AU - Diamond, Michael S.

AU - Ellebedy, Ali H.

PY - 2020/8/15

Y1 - 2020/8/15

N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.

AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.

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SN - 0022-1767

VL - 205

SP - 915

EP - 922

JO - Journal of Immunology

JF - Journal of Immunology

IS - 4

ER -

A potently neutralizing antibody protects mice against SARS-CoV-2 infection

Abstract

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