A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection
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...
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creator | Alsoussi, Wafaa B Turner, Jackson S Case, James B Zhao, Haiyan Schmitz, Aaron J Zhou, Julian Q Chen, Rita E Lei, Tingting Rizk, Amena A McIntire, Katherine M Winkler, Emma S Fox, Julie M Kafai, Natasha M Thackray, Larissa B Hassan, Ahmed O Amanat, Fatima Krammer, Florian Watson, Corey T Kleinstein, Steven H Fremont, Daved H Diamond, Michael S Ellebedy, Ali H |
description | 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 |
doi_str_mv | 10.4049/jimmunol.2000583 |
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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.</description><identifier>ISSN: 0022-1767</identifier><identifier>ISSN: 1550-6606</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.2000583</identifier><identifier>PMID: 32591393</identifier><language>eng</language><publisher>United States</publisher><subject>Angiotensin-Converting Enzyme 2 ; Animals ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - pharmacology ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Neutralizing - immunology ; Antibodies, Neutralizing - pharmacology ; Antibodies, Neutralizing - therapeutic use ; Antibodies, Viral - immunology ; Antibodies, Viral - pharmacology ; Antibodies, Viral - therapeutic use ; Betacoronavirus - drug effects ; Chlorocebus aethiops ; Coronavirus Infections - drug therapy ; Coronavirus Infections - immunology ; Coronavirus Infections - virology ; COVID-19 ; Disease Models, Animal ; Epitope Mapping ; Female ; HEK293 Cells ; Humans ; Immunodominant Epitopes - immunology ; Mice ; Mice, Inbred C57BL ; Pandemics ; Peptidyl-Dipeptidase A - genetics ; Peptidyl-Dipeptidase A - metabolism ; Pneumonia, Viral - drug therapy ; Pneumonia, Viral - immunology ; Pneumonia, Viral - virology ; Protein Interaction Domains and Motifs - genetics ; Protein Interaction Domains and Motifs - immunology ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus - chemistry ; Spike Glycoprotein, Coronavirus - metabolism ; Transfection ; Vero Cells</subject><ispartof>The Journal of immunology (1950), 2020-08, Vol.205 (4), p.915-922</ispartof><rights>Copyright © 2020 by The American Association of Immunologists, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-e3add9bb8d2f36df90fba7b5d0befc2480ed7c1a2c4e56522891e343a3ccc6f3</citedby><cites>FETCH-LOGICAL-c396t-e3add9bb8d2f36df90fba7b5d0befc2480ed7c1a2c4e56522891e343a3ccc6f3</cites><orcidid>0000-0002-3115-3400 ; 0000-0001-7331-5511 ; 0000-0002-8077-6751 ; 0000-0002-9638-1260 ; 0000-0002-4396-6265 ; 0000-0001-9602-2092 ; 0000-0001-7248-8787 ; 0000-0003-0567-738X ; 0000-0002-8544-2689 ; 0000-0001-5123-5537 ; 0000-0003-4121-776X ; 0000-0003-4957-1544</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32591393$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alsoussi, Wafaa B</creatorcontrib><creatorcontrib>Turner, Jackson S</creatorcontrib><creatorcontrib>Case, James B</creatorcontrib><creatorcontrib>Zhao, Haiyan</creatorcontrib><creatorcontrib>Schmitz, Aaron J</creatorcontrib><creatorcontrib>Zhou, Julian Q</creatorcontrib><creatorcontrib>Chen, Rita E</creatorcontrib><creatorcontrib>Lei, Tingting</creatorcontrib><creatorcontrib>Rizk, Amena A</creatorcontrib><creatorcontrib>McIntire, Katherine M</creatorcontrib><creatorcontrib>Winkler, Emma S</creatorcontrib><creatorcontrib>Fox, Julie M</creatorcontrib><creatorcontrib>Kafai, Natasha M</creatorcontrib><creatorcontrib>Thackray, Larissa B</creatorcontrib><creatorcontrib>Hassan, Ahmed O</creatorcontrib><creatorcontrib>Amanat, Fatima</creatorcontrib><creatorcontrib>Krammer, Florian</creatorcontrib><creatorcontrib>Watson, Corey T</creatorcontrib><creatorcontrib>Kleinstein, Steven H</creatorcontrib><creatorcontrib>Fremont, Daved H</creatorcontrib><creatorcontrib>Diamond, Michael S</creatorcontrib><creatorcontrib>Ellebedy, Ali H</creatorcontrib><title>A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>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.</description><subject>Angiotensin-Converting Enzyme 2</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibodies, Neutralizing - pharmacology</subject><subject>Antibodies, Neutralizing - therapeutic use</subject><subject>Antibodies, Viral - immunology</subject><subject>Antibodies, Viral - pharmacology</subject><subject>Antibodies, Viral - therapeutic use</subject><subject>Betacoronavirus - drug effects</subject><subject>Chlorocebus aethiops</subject><subject>Coronavirus Infections - drug therapy</subject><subject>Coronavirus Infections - immunology</subject><subject>Coronavirus Infections - virology</subject><subject>COVID-19</subject><subject>Disease Models, Animal</subject><subject>Epitope Mapping</subject><subject>Female</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Immunodominant Epitopes - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Pandemics</subject><subject>Peptidyl-Dipeptidase A - genetics</subject><subject>Peptidyl-Dipeptidase A - metabolism</subject><subject>Pneumonia, Viral - drug therapy</subject><subject>Pneumonia, Viral - immunology</subject><subject>Pneumonia, Viral - virology</subject><subject>Protein Interaction Domains and Motifs - genetics</subject><subject>Protein Interaction Domains and Motifs - immunology</subject><subject>SARS-CoV-2</subject><subject>Spike Glycoprotein, Coronavirus - chemistry</subject><subject>Spike Glycoprotein, Coronavirus - metabolism</subject><subject>Transfection</subject><subject>Vero Cells</subject><issn>0022-1767</issn><issn>1550-6606</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUTlPwzAYtRCIlsLOhDKypPiInWRBqiqOigIVrVgtx3aKq8QucYJUfj1GPQTTN7zje3oPgEsEhwlM8puVqevOumqIIYQ0I0egjyiFMWOQHYM-hBjHKGVpD5x5vwocBnFyCnoE0xyRnPTB0yiauVbbttpEL7prG1GZb2OX0ci2pnBqE82agMvWR89G6kgshbG-jeajt3k8du8xjia2DLhx9hyclKLy-mJ3B2Bxf7cYP8bT14fJeDSNJclZG2silMqLIlO4JEyVOSwLkRZUwUKXEicZ1CqVSGCZaMooxlmONEmIIFJKVpIBuN3arrui1kqG8CE1XzemFs2GO2H4f8SaD750XzyloZc0CQbXO4PGfXbat7w2XuqqEla7znOcoAxhljEYqHBLlY3zvtHl4Q2C_HcCvp-A7yYIkqu_8Q6CfefkB2cAhf0</recordid><startdate>20200815</startdate><enddate>20200815</enddate><creator>Alsoussi, Wafaa B</creator><creator>Turner, Jackson S</creator><creator>Case, James B</creator><creator>Zhao, Haiyan</creator><creator>Schmitz, Aaron J</creator><creator>Zhou, Julian Q</creator><creator>Chen, Rita E</creator><creator>Lei, Tingting</creator><creator>Rizk, Amena A</creator><creator>McIntire, Katherine M</creator><creator>Winkler, Emma S</creator><creator>Fox, Julie M</creator><creator>Kafai, Natasha M</creator><creator>Thackray, Larissa B</creator><creator>Hassan, Ahmed O</creator><creator>Amanat, Fatima</creator><creator>Krammer, Florian</creator><creator>Watson, Corey T</creator><creator>Kleinstein, Steven H</creator><creator>Fremont, Daved H</creator><creator>Diamond, Michael S</creator><creator>Ellebedy, Ali H</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3115-3400</orcidid><orcidid>https://orcid.org/0000-0001-7331-5511</orcidid><orcidid>https://orcid.org/0000-0002-8077-6751</orcidid><orcidid>https://orcid.org/0000-0002-9638-1260</orcidid><orcidid>https://orcid.org/0000-0002-4396-6265</orcidid><orcidid>https://orcid.org/0000-0001-9602-2092</orcidid><orcidid>https://orcid.org/0000-0001-7248-8787</orcidid><orcidid>https://orcid.org/0000-0003-0567-738X</orcidid><orcidid>https://orcid.org/0000-0002-8544-2689</orcidid><orcidid>https://orcid.org/0000-0001-5123-5537</orcidid><orcidid>https://orcid.org/0000-0003-4121-776X</orcidid><orcidid>https://orcid.org/0000-0003-4957-1544</orcidid></search><sort><creationdate>20200815</creationdate><title>A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection</title><author>Alsoussi, Wafaa B ; Turner, Jackson S ; Case, James B ; Zhao, Haiyan ; Schmitz, Aaron J ; Zhou, Julian Q ; Chen, Rita E ; Lei, Tingting ; Rizk, Amena A ; McIntire, Katherine M ; Winkler, Emma S ; Fox, Julie M ; Kafai, Natasha M ; Thackray, Larissa B ; Hassan, Ahmed O ; Amanat, Fatima ; Krammer, Florian ; Watson, Corey T ; Kleinstein, Steven H ; Fremont, Daved H ; Diamond, Michael S ; Ellebedy, Ali H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-e3add9bb8d2f36df90fba7b5d0befc2480ed7c1a2c4e56522891e343a3ccc6f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Angiotensin-Converting Enzyme 2</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - 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subjects | Angiotensin-Converting Enzyme 2 Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal - therapeutic use Antibodies, Neutralizing - immunology Antibodies, Neutralizing - pharmacology Antibodies, Neutralizing - therapeutic use Antibodies, Viral - immunology Antibodies, Viral - pharmacology Antibodies, Viral - therapeutic use Betacoronavirus - drug effects Chlorocebus aethiops Coronavirus Infections - drug therapy Coronavirus Infections - immunology Coronavirus Infections - virology COVID-19 Disease Models, Animal Epitope Mapping Female HEK293 Cells Humans Immunodominant Epitopes - immunology Mice Mice, Inbred C57BL Pandemics Peptidyl-Dipeptidase A - genetics Peptidyl-Dipeptidase A - metabolism Pneumonia, Viral - drug therapy Pneumonia, Viral - immunology Pneumonia, Viral - virology Protein Interaction Domains and Motifs - genetics Protein Interaction Domains and Motifs - immunology SARS-CoV-2 Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - metabolism Transfection Vero Cells |
title | A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection |
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