Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study
Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2021-10, Vol.374 (6566), p.472-478 |
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| creator | Hastie, Kathryn M Li, Haoyang Bedinger, Daniel Schendel, Sharon L Dennison, S Moses Li, Kan Rayaprolu, Vamseedhar Yu, Xiaoying Mann, Colin Zandonatti, Michelle Diaz Avalos, Ruben Zyla, Dawid Buck, Tierra Hui, Sean Shaffer, Kelly Hariharan, Chitra Yin, Jieyun Olmedillas, Eduardo Enriquez, Adrian Parekh, Diptiben Abraha, Milite Feeney, Elizabeth Horn, Gillian Q Aldon, Yoann Ali, Hanif Aracic, Sanja Cobb, Ronald R Federman, Ross S Fernandez, Joseph M Glanville, Jacob Green, Robin Grigoryan, Gevorg Lujan Hernandez, Ana G Ho, David D Huang, Kuan-Ying A Ingraham, John Jiang, Weidong Kellam, Paul Kim, Cheolmin Kim, Minsoo Kim, Hyeong Mi Kong, Chao Krebs, Shelly J Lan, Fei Lang, Guojun Lee, Sooyoung Leung, Cheuk Lun Liu, Junli Lu, Yanan MacCamy, Anna McGuire, Andrew T Palser, Anne L Rabbitts, Terence H Rikhtegaran Tehrani, Zahra Sajadi, Mohammad M Sanders, Rogier W Sato, Aaron K Schweizer, Liang Seo, Jimin Shen, Bingqing Snitselaar, Jonne L Stamatatos, Leonidas Tan, Yongcong Tomic, Milan T van Gils, Marit J Youssef, Sawsan Yu, Jian Yuan, Tom Z Zhang, Qian Peters, Bjoern Tomaras, Georgia D Germann, Timothy Saphire, Erica Ollmann |
| description | Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy. |
| doi_str_mv | 10.1126/science.abh2315 |
| format | Article |
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Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy.</description><identifier>ISSN: 0036-8075</identifier><identifier>ISSN: 1095-9203</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.abh2315</identifier><identifier>PMID: 34554826</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>Antibodies ; Antibodies, Neutralizing - immunology ; Antibodies, Neutralizing - therapeutic use ; Antibodies, Viral - immunology ; Antibodies, Viral - therapeutic use ; Antigens, Viral - chemistry ; Antigens, Viral - immunology ; Binding ; Community Relations ; Competition ; Consortia ; Coronaviruses ; COVID-19 ; COVID-19 - therapy ; COVID-19 vaccines ; Disease transmission ; Domains ; Epitope Mapping ; Epitopes ; Humans ; Immunodominant Epitopes - chemistry ; Immunodominant Epitopes - immunology ; Infections ; Monoclonal antibodies ; Morbidity ; Mutation ; Neutralization ; Prevention ; Protein Binding ; Protein Domains ; Proteins ; Receptors ; Respiratory diseases ; SARS-CoV-2 - immunology ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Spike Glycoprotein, Coronavirus - chemistry ; Spike Glycoprotein, Coronavirus - immunology ; Spike protein ; Vaccines ; Viral diseases</subject><ispartof>Science (American Association for the Advancement of Science), 2021-10, Vol.374 (6566), p.472-478</ispartof><rights>Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. 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0000-0001-5009-9369 ; 0000-0001-7798-3605 ; 0000-0002-3306-9333 ; 0000-0003-1136-1760 ; 0000-0003-3422-8161 ; 0000-0002-2577-7786 ; 0000-0003-4645-7666 ; 0000-0003-3166-4734 ; 0000-0001-5552-9209 ; 0000-0002-5062-7261 ; 0000-0001-7668-4320 ; 0000-0002-3406-1210 ; 0000-0002-1972-9462 ; 0000-0001-7411-0593 ; 0000-0001-6891-6945 ; 0000-0001-7810-5601 ; 0000-0003-2687-7495 ; 0000-0001-9831-9391 ; 0000-0003-0949-2075 ; 0000-0003-4571-1933 ; 0000-0003-3925-8714 ; 0000-0002-8225-6688 ; 0000-0001-8128-361X ; 0000-0001-8604-4538 ; 0000-0002-5304-1960 ; 0000-0003-1002-6020</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,2871,2872,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34554826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hastie, Kathryn M</creatorcontrib><creatorcontrib>Li, Haoyang</creatorcontrib><creatorcontrib>Bedinger, Daniel</creatorcontrib><creatorcontrib>Schendel, Sharon L</creatorcontrib><creatorcontrib>Dennison, S Moses</creatorcontrib><creatorcontrib>Li, Kan</creatorcontrib><creatorcontrib>Rayaprolu, Vamseedhar</creatorcontrib><creatorcontrib>Yu, Xiaoying</creatorcontrib><creatorcontrib>Mann, Colin</creatorcontrib><creatorcontrib>Zandonatti, Michelle</creatorcontrib><creatorcontrib>Diaz Avalos, Ruben</creatorcontrib><creatorcontrib>Zyla, Dawid</creatorcontrib><creatorcontrib>Buck, Tierra</creatorcontrib><creatorcontrib>Hui, Sean</creatorcontrib><creatorcontrib>Shaffer, Kelly</creatorcontrib><creatorcontrib>Hariharan, Chitra</creatorcontrib><creatorcontrib>Yin, Jieyun</creatorcontrib><creatorcontrib>Olmedillas, Eduardo</creatorcontrib><creatorcontrib>Enriquez, Adrian</creatorcontrib><creatorcontrib>Parekh, Diptiben</creatorcontrib><creatorcontrib>Abraha, Milite</creatorcontrib><creatorcontrib>Feeney, Elizabeth</creatorcontrib><creatorcontrib>Horn, Gillian Q</creatorcontrib><creatorcontrib>Aldon, Yoann</creatorcontrib><creatorcontrib>Ali, Hanif</creatorcontrib><creatorcontrib>Aracic, Sanja</creatorcontrib><creatorcontrib>Cobb, Ronald R</creatorcontrib><creatorcontrib>Federman, Ross S</creatorcontrib><creatorcontrib>Fernandez, Joseph M</creatorcontrib><creatorcontrib>Glanville, Jacob</creatorcontrib><creatorcontrib>Green, Robin</creatorcontrib><creatorcontrib>Grigoryan, Gevorg</creatorcontrib><creatorcontrib>Lujan Hernandez, Ana G</creatorcontrib><creatorcontrib>Ho, David D</creatorcontrib><creatorcontrib>Huang, Kuan-Ying A</creatorcontrib><creatorcontrib>Ingraham, John</creatorcontrib><creatorcontrib>Jiang, Weidong</creatorcontrib><creatorcontrib>Kellam, Paul</creatorcontrib><creatorcontrib>Kim, Cheolmin</creatorcontrib><creatorcontrib>Kim, Minsoo</creatorcontrib><creatorcontrib>Kim, Hyeong Mi</creatorcontrib><creatorcontrib>Kong, Chao</creatorcontrib><creatorcontrib>Krebs, Shelly J</creatorcontrib><creatorcontrib>Lan, Fei</creatorcontrib><creatorcontrib>Lang, Guojun</creatorcontrib><creatorcontrib>Lee, Sooyoung</creatorcontrib><creatorcontrib>Leung, Cheuk Lun</creatorcontrib><creatorcontrib>Liu, Junli</creatorcontrib><creatorcontrib>Lu, Yanan</creatorcontrib><creatorcontrib>MacCamy, Anna</creatorcontrib><creatorcontrib>McGuire, Andrew T</creatorcontrib><creatorcontrib>Palser, Anne L</creatorcontrib><creatorcontrib>Rabbitts, Terence H</creatorcontrib><creatorcontrib>Rikhtegaran Tehrani, Zahra</creatorcontrib><creatorcontrib>Sajadi, Mohammad M</creatorcontrib><creatorcontrib>Sanders, Rogier W</creatorcontrib><creatorcontrib>Sato, Aaron K</creatorcontrib><creatorcontrib>Schweizer, Liang</creatorcontrib><creatorcontrib>Seo, Jimin</creatorcontrib><creatorcontrib>Shen, Bingqing</creatorcontrib><creatorcontrib>Snitselaar, Jonne L</creatorcontrib><creatorcontrib>Stamatatos, Leonidas</creatorcontrib><creatorcontrib>Tan, Yongcong</creatorcontrib><creatorcontrib>Tomic, Milan T</creatorcontrib><creatorcontrib>van Gils, Marit J</creatorcontrib><creatorcontrib>Youssef, Sawsan</creatorcontrib><creatorcontrib>Yu, Jian</creatorcontrib><creatorcontrib>Yuan, Tom Z</creatorcontrib><creatorcontrib>Zhang, Qian</creatorcontrib><creatorcontrib>Peters, Bjoern</creatorcontrib><creatorcontrib>Tomaras, Georgia D</creatorcontrib><creatorcontrib>Germann, Timothy</creatorcontrib><creatorcontrib>Saphire, Erica Ollmann</creatorcontrib><creatorcontrib>CoVIC-DB team1</creatorcontrib><creatorcontrib>CoVIC-DB team</creatorcontrib><title>Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy.</description><subject>Antibodies</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibodies, Neutralizing - therapeutic use</subject><subject>Antibodies, Viral - immunology</subject><subject>Antibodies, Viral - therapeutic use</subject><subject>Antigens, Viral - chemistry</subject><subject>Antigens, Viral - immunology</subject><subject>Binding</subject><subject>Community Relations</subject><subject>Competition</subject><subject>Consortia</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - therapy</subject><subject>COVID-19 vaccines</subject><subject>Disease transmission</subject><subject>Domains</subject><subject>Epitope Mapping</subject><subject>Epitopes</subject><subject>Humans</subject><subject>Immunodominant Epitopes - chemistry</subject><subject>Immunodominant Epitopes - immunology</subject><subject>Infections</subject><subject>Monoclonal antibodies</subject><subject>Morbidity</subject><subject>Mutation</subject><subject>Neutralization</subject><subject>Prevention</subject><subject>Protein Binding</subject><subject>Protein Domains</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Respiratory diseases</subject><subject>SARS-CoV-2 - immunology</subject><subject>Severe acute respiratory syndrome</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Spike Glycoprotein, Coronavirus - chemistry</subject><subject>Spike Glycoprotein, Coronavirus - immunology</subject><subject>Spike protein</subject><subject>Vaccines</subject><subject>Viral 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variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study</title><author>Hastie, Kathryn M ; Li, Haoyang ; Bedinger, Daniel ; Schendel, Sharon L ; Dennison, S Moses ; Li, Kan ; Rayaprolu, Vamseedhar ; Yu, Xiaoying ; Mann, Colin ; Zandonatti, Michelle ; Diaz Avalos, Ruben ; Zyla, Dawid ; Buck, Tierra ; Hui, Sean ; Shaffer, Kelly ; Hariharan, Chitra ; Yin, Jieyun ; Olmedillas, Eduardo ; Enriquez, Adrian ; Parekh, Diptiben ; Abraha, Milite ; Feeney, Elizabeth ; Horn, Gillian Q ; Aldon, Yoann ; Ali, Hanif ; Aracic, Sanja ; Cobb, Ronald R ; Federman, Ross S ; Fernandez, Joseph M ; Glanville, Jacob ; Green, Robin ; Grigoryan, Gevorg ; Lujan Hernandez, Ana G ; Ho, David D ; Huang, Kuan-Ying A ; Ingraham, John ; Jiang, Weidong ; Kellam, Paul ; Kim, Cheolmin ; Kim, Minsoo ; Kim, Hyeong Mi ; Kong, Chao ; Krebs, Shelly J ; Lan, Fei ; Lang, Guojun ; Lee, Sooyoung ; Leung, Cheuk Lun ; Liu, Junli ; Lu, Yanan ; MacCamy, Anna ; McGuire, Andrew T ; Palser, Anne L ; Rabbitts, Terence H ; Rikhtegaran Tehrani, Zahra ; Sajadi, Mohammad M ; Sanders, Rogier W ; Sato, Aaron K ; Schweizer, Liang ; Seo, Jimin ; Shen, Bingqing ; Snitselaar, Jonne L ; Stamatatos, Leonidas ; Tan, Yongcong ; Tomic, Milan T ; van Gils, Marit J ; Youssef, Sawsan ; Yu, Jian ; Yuan, Tom Z ; Zhang, Qian ; Peters, Bjoern ; Tomaras, Georgia D ; Germann, Timothy ; Saphire, Erica Ollmann</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-3f3e35dfff23791825e963ff8cee400ae4c1cc08479c6a90c5707de080fa4df13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies</topic><topic>Antibodies, Neutralizing - immunology</topic><topic>Antibodies, Neutralizing - therapeutic use</topic><topic>Antibodies, Viral - immunology</topic><topic>Antibodies, Viral - therapeutic use</topic><topic>Antigens, Viral - chemistry</topic><topic>Antigens, Viral - immunology</topic><topic>Binding</topic><topic>Community Relations</topic><topic>Competition</topic><topic>Consortia</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 - therapy</topic><topic>COVID-19 vaccines</topic><topic>Disease transmission</topic><topic>Domains</topic><topic>Epitope Mapping</topic><topic>Epitopes</topic><topic>Humans</topic><topic>Immunodominant Epitopes - chemistry</topic><topic>Immunodominant Epitopes - immunology</topic><topic>Infections</topic><topic>Monoclonal antibodies</topic><topic>Morbidity</topic><topic>Mutation</topic><topic>Neutralization</topic><topic>Prevention</topic><topic>Protein Binding</topic><topic>Protein Domains</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Respiratory diseases</topic><topic>SARS-CoV-2 - immunology</topic><topic>Severe acute respiratory syndrome</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Spike Glycoprotein, Coronavirus - chemistry</topic><topic>Spike Glycoprotein, Coronavirus - immunology</topic><topic>Spike protein</topic><topic>Vaccines</topic><topic>Viral diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hastie, Kathryn M</creatorcontrib><creatorcontrib>Li, Haoyang</creatorcontrib><creatorcontrib>Bedinger, Daniel</creatorcontrib><creatorcontrib>Schendel, Sharon L</creatorcontrib><creatorcontrib>Dennison, S Moses</creatorcontrib><creatorcontrib>Li, Kan</creatorcontrib><creatorcontrib>Rayaprolu, Vamseedhar</creatorcontrib><creatorcontrib>Yu, Xiaoying</creatorcontrib><creatorcontrib>Mann, Colin</creatorcontrib><creatorcontrib>Zandonatti, Michelle</creatorcontrib><creatorcontrib>Diaz Avalos, Ruben</creatorcontrib><creatorcontrib>Zyla, Dawid</creatorcontrib><creatorcontrib>Buck, Tierra</creatorcontrib><creatorcontrib>Hui, Sean</creatorcontrib><creatorcontrib>Shaffer, Kelly</creatorcontrib><creatorcontrib>Hariharan, Chitra</creatorcontrib><creatorcontrib>Yin, 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Sean</au><au>Shaffer, Kelly</au><au>Hariharan, Chitra</au><au>Yin, Jieyun</au><au>Olmedillas, Eduardo</au><au>Enriquez, Adrian</au><au>Parekh, Diptiben</au><au>Abraha, Milite</au><au>Feeney, Elizabeth</au><au>Horn, Gillian Q</au><au>Aldon, Yoann</au><au>Ali, Hanif</au><au>Aracic, Sanja</au><au>Cobb, Ronald R</au><au>Federman, Ross S</au><au>Fernandez, Joseph M</au><au>Glanville, Jacob</au><au>Green, Robin</au><au>Grigoryan, Gevorg</au><au>Lujan Hernandez, Ana G</au><au>Ho, David D</au><au>Huang, Kuan-Ying A</au><au>Ingraham, John</au><au>Jiang, Weidong</au><au>Kellam, Paul</au><au>Kim, Cheolmin</au><au>Kim, Minsoo</au><au>Kim, Hyeong Mi</au><au>Kong, Chao</au><au>Krebs, Shelly J</au><au>Lan, Fei</au><au>Lang, Guojun</au><au>Lee, Sooyoung</au><au>Leung, Cheuk Lun</au><au>Liu, Junli</au><au>Lu, Yanan</au><au>MacCamy, Anna</au><au>McGuire, Andrew T</au><au>Palser, Anne L</au><au>Rabbitts, Terence H</au><au>Rikhtegaran Tehrani, Zahra</au><au>Sajadi, Mohammad M</au><au>Sanders, Rogier 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therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. 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| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2021-10, Vol.374 (6566), p.472-478 |
| issn | 0036-8075 1095-9203 1095-9203 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9302186 |
| source | MEDLINE; Science Magazine |
| subjects | Antibodies Antibodies, Neutralizing - immunology Antibodies, Neutralizing - therapeutic use Antibodies, Viral - immunology Antibodies, Viral - therapeutic use Antigens, Viral - chemistry Antigens, Viral - immunology Binding Community Relations Competition Consortia Coronaviruses COVID-19 COVID-19 - therapy COVID-19 vaccines Disease transmission Domains Epitope Mapping Epitopes Humans Immunodominant Epitopes - chemistry Immunodominant Epitopes - immunology Infections Monoclonal antibodies Morbidity Mutation Neutralization Prevention Protein Binding Protein Domains Proteins Receptors Respiratory diseases SARS-CoV-2 - immunology Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - immunology Spike protein Vaccines Viral diseases |
| title | Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T08%3A51%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Defining%20variant-resistant%20epitopes%20targeted%20by%20SARS-CoV-2%20antibodies:%20A%20global%20consortium%20study&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Hastie,%20Kathryn%20M&rft.aucorp=CoVIC-DB%20team1&rft.date=2021-10-22&rft.volume=374&rft.issue=6566&rft.spage=472&rft.epage=478&rft.pages=472-478&rft.issn=0036-8075&rft.eissn=1095-9203&rft_id=info:doi/10.1126/science.abh2315&rft_dat=%3Cproquest_pubme%3E2638084468%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2638084468&rft_id=info:pmid/34554826&rfr_iscdi=true |