Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD
Several potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activi...
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| Veröffentlicht in: | Cell reports (Cambridge) 2021-02, Vol.34 (5), p.108699-108699, Article 108699 |
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| creator | Zhou, Yunjiao Liu, Zezhong Li, Shibo Xu, Wei Zhang, Qianqian Silva, Israel T. Li, Cheng Wu, Yanling Jiang, Qingling Liu, Zhenmi Wang, Qiujing Guo, Yu Wu, Jianbo Gu, Chengjian Cai, Xia Qu, Di Mayer, Christian T. Wang, Xiangxi Jiang, Shibo Ying, Tianlei Yuan, Zhenghong Xie, Youhua Wen, Yumei Lu, Lu Wang, Qiao |
| description | Several potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. Here, we select a convalescent individual with potent IgG neutralizing activity and characterize his antibody response. Monoclonal antibodies isolated from memory B cells target four groups of five non-overlapping receptor-binding domain (RBD) epitopes. Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcγ receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE, while antibodies against the fourth epitope group are poorly neutralizing. One antibody, XG014, potently cross-neutralizes SARS-CoV-2 variants, as well as SARS-CoV-1, with respective IC50 (50% inhibitory concentration) values as low as 5.1 and 23.7 ng/mL, while not exhibiting ADE. Therefore, neutralization and ADE of human SARS-CoV-2 antibodies correlate with non-overlapping RBD epitopes.
[Display omitted]
•Antibodies against SARS-CoV-2 S protein are isolated from an elite neutralizer•Receptor-binding domain (RBD) antibodies target four groups of non-overlapping epitopes•Group IV antibodies induce antibody-dependent enhancement (ADE) of entry in Raji cells•Group II/III antibodies neutralize SARS-CoV-2 without mediating ADE of entry in vitro
Zhou et al. clone human antibodies against the SARS-CoV-2 S protein from an elite neutralizer and reveal the association of antibody-dependent enhancement (ADE)/neutralizing activities in vitro with four distinct groups of non-overlapping epitopes on the receptor-binding domain (RBD). |
| doi_str_mv | 10.1016/j.celrep.2021.108699 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7802522</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S2211124721000127</els_id><sourcerecordid>S2211124721000127</sourcerecordid><originalsourceid>FETCH-LOGICAL-c463t-f6731d62842083508826c4640d9b7249b7ecd6b918119c00c7e9be858a6d993</originalsourceid><addsrcrecordid>eNp9kc9uGyEQxlHVKo7cvEEU8QLrAMuy7CVS6uafFKlSXOWKWBjXWDasALtyb3nzYLlJ3Es5wGiG75sZ_RA6p2RCCRWXy4mBVYRhwgijJSVF131Cp4xRWlHG289H8QidpbQk5QhCacdP0KiuuWw4aU7Ry41faG9gDT7jLcS0SdjDJke9cn90dsHjfodn10-zahqeK4a1z64P1kHC8xjWWGMT_FavIJm9hQ0-RKxTCsbpXD79dnmBrUvZeZMxDC6HoaSLb14Afvr2_Sv6MterBGd_3zGa3d78nN5Xjz_uHqbXj5Xhos7VXLQ1tYJJzoisGyIlE6XCie36lvFygbGi76gsOxpCTAtdD7KRWtiuq8fo6uA6bPo12P2sZUU1RLfWcaeCdurfincL9StsVSsJaxgrBvxgYGJIKcL8XUuJ2jNRS3VgovZM1IFJkV0c930XvRH4GAzK7lsHUSXjoBCxLoLJygb3_w6v9LyhYg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Cell Press Free Archives</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Zhou, Yunjiao ; Liu, Zezhong ; Li, Shibo ; Xu, Wei ; Zhang, Qianqian ; Silva, Israel T. ; Li, Cheng ; Wu, Yanling ; Jiang, Qingling ; Liu, Zhenmi ; Wang, Qiujing ; Guo, Yu ; Wu, Jianbo ; Gu, Chengjian ; Cai, Xia ; Qu, Di ; Mayer, Christian T. ; Wang, Xiangxi ; Jiang, Shibo ; Ying, Tianlei ; Yuan, Zhenghong ; Xie, Youhua ; Wen, Yumei ; Lu, Lu ; Wang, Qiao</creator><creatorcontrib>Zhou, Yunjiao ; Liu, Zezhong ; Li, Shibo ; Xu, Wei ; Zhang, Qianqian ; Silva, Israel T. ; Li, Cheng ; Wu, Yanling ; Jiang, Qingling ; Liu, Zhenmi ; Wang, Qiujing ; Guo, Yu ; Wu, Jianbo ; Gu, Chengjian ; Cai, Xia ; Qu, Di ; Mayer, Christian T. ; Wang, Xiangxi ; Jiang, Shibo ; Ying, Tianlei ; Yuan, Zhenghong ; Xie, Youhua ; Wen, Yumei ; Lu, Lu ; Wang, Qiao</creatorcontrib><description>Several potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. Here, we select a convalescent individual with potent IgG neutralizing activity and characterize his antibody response. Monoclonal antibodies isolated from memory B cells target four groups of five non-overlapping receptor-binding domain (RBD) epitopes. Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcγ receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE, while antibodies against the fourth epitope group are poorly neutralizing. One antibody, XG014, potently cross-neutralizes SARS-CoV-2 variants, as well as SARS-CoV-1, with respective IC50 (50% inhibitory concentration) values as low as 5.1 and 23.7 ng/mL, while not exhibiting ADE. Therefore, neutralization and ADE of human SARS-CoV-2 antibodies correlate with non-overlapping RBD epitopes.
[Display omitted]
•Antibodies against SARS-CoV-2 S protein are isolated from an elite neutralizer•Receptor-binding domain (RBD) antibodies target four groups of non-overlapping epitopes•Group IV antibodies induce antibody-dependent enhancement (ADE) of entry in Raji cells•Group II/III antibodies neutralize SARS-CoV-2 without mediating ADE of entry in vitro
Zhou et al. clone human antibodies against the SARS-CoV-2 S protein from an elite neutralizer and reveal the association of antibody-dependent enhancement (ADE)/neutralizing activities in vitro with four distinct groups of non-overlapping epitopes on the receptor-binding domain (RBD).</description><identifier>ISSN: 2211-1247</identifier><identifier>EISSN: 2211-1247</identifier><identifier>DOI: 10.1016/j.celrep.2021.108699</identifier><identifier>PMID: 33485405</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Antibodies, Monoclonal - immunology ; Antibodies, Neutralizing - immunology ; Antibodies, Viral - immunology ; Antibodies, Viral - therapeutic use ; Antibody-Dependent Enhancement ; Antigen-Antibody Reactions ; Cell Line ; Child ; Cluster Analysis ; COVID-19 - drug therapy ; COVID-19 - immunology ; COVID-19 - virology ; Epitopes - immunology ; Female ; Humans ; Inhibitory Concentration 50 ; Male ; Middle Aged ; neutralizing activity ; Protein Domains - immunology ; receptor-binding domain epitope ; SARS-CoV-1 ; SARS-CoV-2 ; SARS-CoV-2 - isolation & purification ; Spike Glycoprotein, Coronavirus - chemistry ; Spike Glycoprotein, Coronavirus - immunology ; Young Adult</subject><ispartof>Cell reports (Cambridge), 2021-02, Vol.34 (5), p.108699-108699, Article 108699</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.</rights><rights>2021 The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-f6731d62842083508826c4640d9b7249b7ecd6b918119c00c7e9be858a6d993</citedby><cites>FETCH-LOGICAL-c463t-f6731d62842083508826c4640d9b7249b7ecd6b918119c00c7e9be858a6d993</cites><orcidid>0000-0002-0937-3570 ; 0000-0002-8109-7515 ; 0000-0003-3013-7182 ; 0000-0002-7394-8084 ; 0000-0003-0862-8380 ; 0000-0001-8283-7135 ; 0000-0002-4687-1499 ; 0000-0002-3726-4742 ; 0000-0001-6416-1733 ; 0000-0003-2996-2310</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,860,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33485405$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Yunjiao</creatorcontrib><creatorcontrib>Liu, Zezhong</creatorcontrib><creatorcontrib>Li, Shibo</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Zhang, Qianqian</creatorcontrib><creatorcontrib>Silva, Israel T.</creatorcontrib><creatorcontrib>Li, Cheng</creatorcontrib><creatorcontrib>Wu, Yanling</creatorcontrib><creatorcontrib>Jiang, Qingling</creatorcontrib><creatorcontrib>Liu, Zhenmi</creatorcontrib><creatorcontrib>Wang, Qiujing</creatorcontrib><creatorcontrib>Guo, Yu</creatorcontrib><creatorcontrib>Wu, Jianbo</creatorcontrib><creatorcontrib>Gu, Chengjian</creatorcontrib><creatorcontrib>Cai, Xia</creatorcontrib><creatorcontrib>Qu, Di</creatorcontrib><creatorcontrib>Mayer, Christian T.</creatorcontrib><creatorcontrib>Wang, Xiangxi</creatorcontrib><creatorcontrib>Jiang, Shibo</creatorcontrib><creatorcontrib>Ying, Tianlei</creatorcontrib><creatorcontrib>Yuan, Zhenghong</creatorcontrib><creatorcontrib>Xie, Youhua</creatorcontrib><creatorcontrib>Wen, Yumei</creatorcontrib><creatorcontrib>Lu, Lu</creatorcontrib><creatorcontrib>Wang, Qiao</creatorcontrib><title>Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD</title><title>Cell reports (Cambridge)</title><addtitle>Cell Rep</addtitle><description>Several potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. Here, we select a convalescent individual with potent IgG neutralizing activity and characterize his antibody response. Monoclonal antibodies isolated from memory B cells target four groups of five non-overlapping receptor-binding domain (RBD) epitopes. Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcγ receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE, while antibodies against the fourth epitope group are poorly neutralizing. One antibody, XG014, potently cross-neutralizes SARS-CoV-2 variants, as well as SARS-CoV-1, with respective IC50 (50% inhibitory concentration) values as low as 5.1 and 23.7 ng/mL, while not exhibiting ADE. Therefore, neutralization and ADE of human SARS-CoV-2 antibodies correlate with non-overlapping RBD epitopes.
[Display omitted]
•Antibodies against SARS-CoV-2 S protein are isolated from an elite neutralizer•Receptor-binding domain (RBD) antibodies target four groups of non-overlapping epitopes•Group IV antibodies induce antibody-dependent enhancement (ADE) of entry in Raji cells•Group II/III antibodies neutralize SARS-CoV-2 without mediating ADE of entry in vitro
Zhou et al. clone human antibodies against the SARS-CoV-2 S protein from an elite neutralizer and reveal the association of antibody-dependent enhancement (ADE)/neutralizing activities in vitro with four distinct groups of non-overlapping epitopes on the receptor-binding domain (RBD).</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibodies, Viral - immunology</subject><subject>Antibodies, Viral - therapeutic use</subject><subject>Antibody-Dependent Enhancement</subject><subject>Antigen-Antibody Reactions</subject><subject>Cell Line</subject><subject>Child</subject><subject>Cluster Analysis</subject><subject>COVID-19 - drug therapy</subject><subject>COVID-19 - immunology</subject><subject>COVID-19 - virology</subject><subject>Epitopes - immunology</subject><subject>Female</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Male</subject><subject>Middle Aged</subject><subject>neutralizing activity</subject><subject>Protein Domains - immunology</subject><subject>receptor-binding domain epitope</subject><subject>SARS-CoV-1</subject><subject>SARS-CoV-2</subject><subject>SARS-CoV-2 - isolation & purification</subject><subject>Spike Glycoprotein, Coronavirus - chemistry</subject><subject>Spike Glycoprotein, Coronavirus - immunology</subject><subject>Young Adult</subject><issn>2211-1247</issn><issn>2211-1247</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9uGyEQxlHVKo7cvEEU8QLrAMuy7CVS6uafFKlSXOWKWBjXWDasALtyb3nzYLlJ3Es5wGiG75sZ_RA6p2RCCRWXy4mBVYRhwgijJSVF131Cp4xRWlHG289H8QidpbQk5QhCacdP0KiuuWw4aU7Ry41faG9gDT7jLcS0SdjDJke9cn90dsHjfodn10-zahqeK4a1z64P1kHC8xjWWGMT_FavIJm9hQ0-RKxTCsbpXD79dnmBrUvZeZMxDC6HoaSLb14Afvr2_Sv6MterBGd_3zGa3d78nN5Xjz_uHqbXj5Xhos7VXLQ1tYJJzoisGyIlE6XCie36lvFygbGi76gsOxpCTAtdD7KRWtiuq8fo6uA6bPo12P2sZUU1RLfWcaeCdurfincL9StsVSsJaxgrBvxgYGJIKcL8XUuJ2jNRS3VgovZM1IFJkV0c930XvRH4GAzK7lsHUSXjoBCxLoLJygb3_w6v9LyhYg</recordid><startdate>20210202</startdate><enddate>20210202</enddate><creator>Zhou, Yunjiao</creator><creator>Liu, Zezhong</creator><creator>Li, Shibo</creator><creator>Xu, Wei</creator><creator>Zhang, Qianqian</creator><creator>Silva, Israel T.</creator><creator>Li, Cheng</creator><creator>Wu, Yanling</creator><creator>Jiang, Qingling</creator><creator>Liu, Zhenmi</creator><creator>Wang, Qiujing</creator><creator>Guo, Yu</creator><creator>Wu, Jianbo</creator><creator>Gu, Chengjian</creator><creator>Cai, Xia</creator><creator>Qu, Di</creator><creator>Mayer, Christian T.</creator><creator>Wang, Xiangxi</creator><creator>Jiang, Shibo</creator><creator>Ying, Tianlei</creator><creator>Yuan, Zhenghong</creator><creator>Xie, Youhua</creator><creator>Wen, Yumei</creator><creator>Lu, Lu</creator><creator>Wang, Qiao</creator><general>Elsevier Inc</general><general>The Author(s)</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope><orcidid>https://orcid.org/0000-0002-0937-3570</orcidid><orcidid>https://orcid.org/0000-0002-8109-7515</orcidid><orcidid>https://orcid.org/0000-0003-3013-7182</orcidid><orcidid>https://orcid.org/0000-0002-7394-8084</orcidid><orcidid>https://orcid.org/0000-0003-0862-8380</orcidid><orcidid>https://orcid.org/0000-0001-8283-7135</orcidid><orcidid>https://orcid.org/0000-0002-4687-1499</orcidid><orcidid>https://orcid.org/0000-0002-3726-4742</orcidid><orcidid>https://orcid.org/0000-0001-6416-1733</orcidid><orcidid>https://orcid.org/0000-0003-2996-2310</orcidid></search><sort><creationdate>20210202</creationdate><title>Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD</title><author>Zhou, Yunjiao ; Liu, Zezhong ; Li, Shibo ; Xu, Wei ; Zhang, Qianqian ; Silva, Israel T. ; Li, Cheng ; Wu, Yanling ; Jiang, Qingling ; Liu, Zhenmi ; Wang, Qiujing ; Guo, Yu ; Wu, Jianbo ; Gu, Chengjian ; Cai, Xia ; Qu, Di ; Mayer, Christian T. ; Wang, Xiangxi ; Jiang, Shibo ; Ying, Tianlei ; Yuan, Zhenghong ; Xie, Youhua ; Wen, Yumei ; Lu, Lu ; Wang, Qiao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-f6731d62842083508826c4640d9b7249b7ecd6b918119c00c7e9be858a6d993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Neutralizing - immunology</topic><topic>Antibodies, Viral - immunology</topic><topic>Antibodies, Viral - therapeutic use</topic><topic>Antibody-Dependent Enhancement</topic><topic>Antigen-Antibody Reactions</topic><topic>Cell Line</topic><topic>Child</topic><topic>Cluster Analysis</topic><topic>COVID-19 - drug therapy</topic><topic>COVID-19 - immunology</topic><topic>COVID-19 - virology</topic><topic>Epitopes - immunology</topic><topic>Female</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>Male</topic><topic>Middle Aged</topic><topic>neutralizing activity</topic><topic>Protein Domains - immunology</topic><topic>receptor-binding domain epitope</topic><topic>SARS-CoV-1</topic><topic>SARS-CoV-2</topic><topic>SARS-CoV-2 - isolation & purification</topic><topic>Spike Glycoprotein, Coronavirus - chemistry</topic><topic>Spike Glycoprotein, Coronavirus - immunology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Yunjiao</creatorcontrib><creatorcontrib>Liu, Zezhong</creatorcontrib><creatorcontrib>Li, Shibo</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Zhang, Qianqian</creatorcontrib><creatorcontrib>Silva, Israel T.</creatorcontrib><creatorcontrib>Li, Cheng</creatorcontrib><creatorcontrib>Wu, Yanling</creatorcontrib><creatorcontrib>Jiang, Qingling</creatorcontrib><creatorcontrib>Liu, Zhenmi</creatorcontrib><creatorcontrib>Wang, Qiujing</creatorcontrib><creatorcontrib>Guo, Yu</creatorcontrib><creatorcontrib>Wu, Jianbo</creatorcontrib><creatorcontrib>Gu, Chengjian</creatorcontrib><creatorcontrib>Cai, Xia</creatorcontrib><creatorcontrib>Qu, Di</creatorcontrib><creatorcontrib>Mayer, Christian T.</creatorcontrib><creatorcontrib>Wang, Xiangxi</creatorcontrib><creatorcontrib>Jiang, Shibo</creatorcontrib><creatorcontrib>Ying, Tianlei</creatorcontrib><creatorcontrib>Yuan, Zhenghong</creatorcontrib><creatorcontrib>Xie, Youhua</creatorcontrib><creatorcontrib>Wen, Yumei</creatorcontrib><creatorcontrib>Lu, Lu</creatorcontrib><creatorcontrib>Wang, Qiao</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell reports (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Yunjiao</au><au>Liu, Zezhong</au><au>Li, Shibo</au><au>Xu, Wei</au><au>Zhang, Qianqian</au><au>Silva, Israel T.</au><au>Li, Cheng</au><au>Wu, Yanling</au><au>Jiang, Qingling</au><au>Liu, Zhenmi</au><au>Wang, Qiujing</au><au>Guo, Yu</au><au>Wu, Jianbo</au><au>Gu, Chengjian</au><au>Cai, Xia</au><au>Qu, Di</au><au>Mayer, Christian T.</au><au>Wang, Xiangxi</au><au>Jiang, Shibo</au><au>Ying, Tianlei</au><au>Yuan, Zhenghong</au><au>Xie, Youhua</au><au>Wen, Yumei</au><au>Lu, Lu</au><au>Wang, Qiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD</atitle><jtitle>Cell reports (Cambridge)</jtitle><addtitle>Cell Rep</addtitle><date>2021-02-02</date><risdate>2021</risdate><volume>34</volume><issue>5</issue><spage>108699</spage><epage>108699</epage><pages>108699-108699</pages><artnum>108699</artnum><issn>2211-1247</issn><eissn>2211-1247</eissn><abstract>Several potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. Here, we select a convalescent individual with potent IgG neutralizing activity and characterize his antibody response. Monoclonal antibodies isolated from memory B cells target four groups of five non-overlapping receptor-binding domain (RBD) epitopes. Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcγ receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE, while antibodies against the fourth epitope group are poorly neutralizing. One antibody, XG014, potently cross-neutralizes SARS-CoV-2 variants, as well as SARS-CoV-1, with respective IC50 (50% inhibitory concentration) values as low as 5.1 and 23.7 ng/mL, while not exhibiting ADE. Therefore, neutralization and ADE of human SARS-CoV-2 antibodies correlate with non-overlapping RBD epitopes.
[Display omitted]
•Antibodies against SARS-CoV-2 S protein are isolated from an elite neutralizer•Receptor-binding domain (RBD) antibodies target four groups of non-overlapping epitopes•Group IV antibodies induce antibody-dependent enhancement (ADE) of entry in Raji cells•Group II/III antibodies neutralize SARS-CoV-2 without mediating ADE of entry in vitro
Zhou et al. clone human antibodies against the SARS-CoV-2 S protein from an elite neutralizer and reveal the association of antibody-dependent enhancement (ADE)/neutralizing activities in vitro with four distinct groups of non-overlapping epitopes on the receptor-binding domain (RBD).</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33485405</pmid><doi>10.1016/j.celrep.2021.108699</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0937-3570</orcidid><orcidid>https://orcid.org/0000-0002-8109-7515</orcidid><orcidid>https://orcid.org/0000-0003-3013-7182</orcidid><orcidid>https://orcid.org/0000-0002-7394-8084</orcidid><orcidid>https://orcid.org/0000-0003-0862-8380</orcidid><orcidid>https://orcid.org/0000-0001-8283-7135</orcidid><orcidid>https://orcid.org/0000-0002-4687-1499</orcidid><orcidid>https://orcid.org/0000-0002-3726-4742</orcidid><orcidid>https://orcid.org/0000-0001-6416-1733</orcidid><orcidid>https://orcid.org/0000-0003-2996-2310</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2211-1247 |
| ispartof | Cell reports (Cambridge), 2021-02, Vol.34 (5), p.108699-108699, Article 108699 |
| issn | 2211-1247 2211-1247 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Antibodies, Monoclonal - immunology Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Antibodies, Viral - therapeutic use Antibody-Dependent Enhancement Antigen-Antibody Reactions Cell Line Child Cluster Analysis COVID-19 - drug therapy COVID-19 - immunology COVID-19 - virology Epitopes - immunology Female Humans Inhibitory Concentration 50 Male Middle Aged neutralizing activity Protein Domains - immunology receptor-binding domain epitope SARS-CoV-1 SARS-CoV-2 SARS-CoV-2 - isolation & purification Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - immunology Young Adult |
| title | Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T12%3A39%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Enhancement%20versus%20neutralization%20by%20SARS-CoV-2%20antibodies%20from%20a%20convalescent%20donor%20associates%20with%20distinct%20epitopes%20on%20the%20RBD&rft.jtitle=Cell%20reports%20(Cambridge)&rft.au=Zhou,%20Yunjiao&rft.date=2021-02-02&rft.volume=34&rft.issue=5&rft.spage=108699&rft.epage=108699&rft.pages=108699-108699&rft.artnum=108699&rft.issn=2211-1247&rft.eissn=2211-1247&rft_id=info:doi/10.1016/j.celrep.2021.108699&rft_dat=%3Celsevier_pubme%3ES2211124721000127%3C/elsevier_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/33485405&rft_els_id=S2211124721000127&rfr_iscdi=true |