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A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection.
J Immunol. 2020 08 15; 205(4):915-922.JI

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.

Authors+Show Affiliations

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.Interdepartmental Program in Computational Biology and Bioinformatics, Yale School of Medicine, Yale University, New Haven, CT 06511.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10024. Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10024.Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10024.Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40292.Interdepartmental Program in Computational Biology and Bioinformatics, Yale School of Medicine, Yale University, New Haven, CT 06511. Department of Pathology, Yale School of Medicine, New Haven, CT 06511. Department of Immunobiology, Yale School of Medicine, New Haven, CT 06511.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110; and.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110. The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; ellebedy@wustl.edu. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110. The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32591393

Citation

Alsoussi, Wafaa B., et al. "A Potently Neutralizing Antibody Protects Mice Against SARS-CoV-2 Infection." Journal of Immunology (Baltimore, Md. : 1950), vol. 205, no. 4, 2020, pp. 915-922.
Alsoussi WB, Turner JS, Case JB, et al. A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection. J Immunol. 2020;205(4):915-922.
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 (Baltimore, Md. : 1950), 205(4), 915-922. https://doi.org/10.4049/jimmunol.2000583
Alsoussi WB, et al. A Potently Neutralizing Antibody Protects Mice Against SARS-CoV-2 Infection. J Immunol. 2020 08 15;205(4):915-922. PubMed PMID: 32591393.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2020/06/26/ PY - 2020/05/19/received PY - 2020/06/08/accepted PY - 2020/6/28/pubmed PY - 2020/8/29/medline PY - 2020/6/28/entrez SP - 915 EP - 922 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 205 IS - 4 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/32591393/A_Potently_Neutralizing_Antibody_Protects_Mice_against_SARS_CoV_2_Infection_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&amp;pmid=32591393 DB - PRIME DP - Unbound Medicine ER -