Broad neutralization of SARS-related viruses by human monoclonal antibodies
Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 20...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2020-08, Vol.369 (6504), p.731-736 |
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| creator | Wec, Anna Z Wrapp, Daniel Herbert, Andrew S Maurer, Daniel P Haslwanter, Denise Sakharkar, Mrunal Jangra, Rohit K Dieterle, M Eugenia Lilov, Asparouh Huang, Deli Tse, Longping V Johnson, Nicole V Hsieh, Ching-Lin Wang, Nianshuang Nett, Juergen H Champney, Elizabeth Burnina, Irina Brown, Michael Lin, Shu Sinclair, Melanie Johnson, Carl Pudi, Sarat Bortz, 3rd, Robert Wirchnianski, Ariel S Laudermilch, Ethan Florez, Catalina Fels, J Maximilian O'Brien, Cecilia M Graham, Barney S Nemazee, David Burton, Dennis R Baric, Ralph S Voss, James E Chandran, Kartik Dye, John M McLellan, Jason S Walker, Laura M |
| description | Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines. |
| doi_str_mv | 10.1126/science.abc7424 |
| format | Article |
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To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.abc7424</identifier><identifier>PMID: 32540900</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>ACE2 ; Adult ; Aged ; Angiotensin ; Angiotensin-Converting Enzyme 2 ; Antibodies ; Antibodies, Monoclonal - immunology ; Antibodies, Viral - immunology ; Antibody Affinity ; B-Lymphocyte Subsets - immunology ; Betacoronavirus - immunology ; Binding ; Binding Sites ; Broadly Neutralizing Antibodies - immunology ; Coronaviridae ; Coronaviruses ; COVID-19 ; Cross Reactions ; Epitopes ; Female ; Humans ; Immunologic Memory ; Immunological memory ; Immunology ; Lymphocytes B ; Male ; Memory ; Memory cells ; Microbio ; Middle Aged ; Monoclonal antibodies ; Neutralization ; Neutralization Tests ; Neutralizing ; Peptidyl-dipeptidase A ; Peptidyl-Dipeptidase A - chemistry ; Peptidyl-Dipeptidase A - metabolism ; Protein Domains ; Proteins ; Receptors ; Receptors, Coronavirus ; Receptors, Virus - chemistry ; Receptors, Virus - metabolism ; Respiratory diseases ; Sarbecovirus ; SARS-CoV-2 ; Severe Acute Respiratory Syndrome - immunology ; Severe acute respiratory syndrome coronavirus 2 ; Severe acute respiratory syndrome-related coronavirus - immunology ; Somatic hypermutation ; Somatic Hypermutation, Immunoglobulin ; Spike Glycoprotein, Coronavirus - chemistry ; Spike Glycoprotein, Coronavirus - immunology ; Spike Glycoprotein, Coronavirus - metabolism ; Spike protein ; Vaccines ; Viral diseases ; Viruses ; Young Adult</subject><ispartof>Science (American Association for the Advancement of Science), 2020-08, Vol.369 (6504), p.731-736</ispartof><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</rights><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works</rights><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works 2020 American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-b05d66febe5f6a94b4efe65b94d9ab9d1058842621c6ae98eb0a07a8d7734b3</citedby><cites>FETCH-LOGICAL-c515t-b05d66febe5f6a94b4efe65b94d9ab9d1058842621c6ae98eb0a07a8d7734b3</cites><orcidid>0000-0002-0883-5016 ; 0000-0002-4769-6311 ; 0000-0003-4351-125X ; 0000-0002-3953-8954 ; 0000-0002-0538-9647 ; 0000-0002-7569-011X ; 0000-0002-2134-2152 ; 0000-0002-4698-7264 ; 0000-0001-7582-8396 ; 0000-0002-1410-683X ; 0000-0003-2727-0468 ; 0000-0003-3400-7203 ; 0000-0002-4777-1596 ; 0000-0002-0407-861X ; 0000-0001-7160-0220 ; 0000-0001-8112-0853 ; 0000-0003-1751-2152 ; 0000-0001-7704-3197 ; 0000-0003-1455-9318 ; 0000-0003-3292-2117 ; 0000-0001-6711-9864 ; 0000-0002-3119-0869 ; 0000-0002-5257-7253 ; 0000-0003-4697-7928 ; 0000-0001-6827-8701 ; 0000-0003-3991-542X ; 0000-0002-6989-639X</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/32540900$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wec, Anna Z</creatorcontrib><creatorcontrib>Wrapp, Daniel</creatorcontrib><creatorcontrib>Herbert, Andrew S</creatorcontrib><creatorcontrib>Maurer, Daniel P</creatorcontrib><creatorcontrib>Haslwanter, Denise</creatorcontrib><creatorcontrib>Sakharkar, Mrunal</creatorcontrib><creatorcontrib>Jangra, Rohit K</creatorcontrib><creatorcontrib>Dieterle, M Eugenia</creatorcontrib><creatorcontrib>Lilov, Asparouh</creatorcontrib><creatorcontrib>Huang, Deli</creatorcontrib><creatorcontrib>Tse, Longping V</creatorcontrib><creatorcontrib>Johnson, Nicole V</creatorcontrib><creatorcontrib>Hsieh, Ching-Lin</creatorcontrib><creatorcontrib>Wang, Nianshuang</creatorcontrib><creatorcontrib>Nett, Juergen H</creatorcontrib><creatorcontrib>Champney, Elizabeth</creatorcontrib><creatorcontrib>Burnina, Irina</creatorcontrib><creatorcontrib>Brown, Michael</creatorcontrib><creatorcontrib>Lin, Shu</creatorcontrib><creatorcontrib>Sinclair, Melanie</creatorcontrib><creatorcontrib>Johnson, Carl</creatorcontrib><creatorcontrib>Pudi, Sarat</creatorcontrib><creatorcontrib>Bortz, 3rd, Robert</creatorcontrib><creatorcontrib>Wirchnianski, Ariel S</creatorcontrib><creatorcontrib>Laudermilch, Ethan</creatorcontrib><creatorcontrib>Florez, Catalina</creatorcontrib><creatorcontrib>Fels, J Maximilian</creatorcontrib><creatorcontrib>O'Brien, Cecilia M</creatorcontrib><creatorcontrib>Graham, Barney S</creatorcontrib><creatorcontrib>Nemazee, David</creatorcontrib><creatorcontrib>Burton, Dennis R</creatorcontrib><creatorcontrib>Baric, Ralph S</creatorcontrib><creatorcontrib>Voss, James E</creatorcontrib><creatorcontrib>Chandran, Kartik</creatorcontrib><creatorcontrib>Dye, John M</creatorcontrib><creatorcontrib>McLellan, Jason S</creatorcontrib><creatorcontrib>Walker, Laura M</creatorcontrib><title>Broad neutralization of SARS-related viruses by human monoclonal antibodies</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.</description><subject>ACE2</subject><subject>Adult</subject><subject>Aged</subject><subject>Angiotensin</subject><subject>Angiotensin-Converting Enzyme 2</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Viral - immunology</subject><subject>Antibody Affinity</subject><subject>B-Lymphocyte Subsets - immunology</subject><subject>Betacoronavirus - immunology</subject><subject>Binding</subject><subject>Binding Sites</subject><subject>Broadly Neutralizing Antibodies - immunology</subject><subject>Coronaviridae</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Cross Reactions</subject><subject>Epitopes</subject><subject>Female</subject><subject>Humans</subject><subject>Immunologic Memory</subject><subject>Immunological memory</subject><subject>Immunology</subject><subject>Lymphocytes B</subject><subject>Male</subject><subject>Memory</subject><subject>Memory cells</subject><subject>Microbio</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Neutralization</subject><subject>Neutralization Tests</subject><subject>Neutralizing</subject><subject>Peptidyl-dipeptidase A</subject><subject>Peptidyl-Dipeptidase A - chemistry</subject><subject>Peptidyl-Dipeptidase A - metabolism</subject><subject>Protein Domains</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Receptors, Coronavirus</subject><subject>Receptors, Virus - chemistry</subject><subject>Receptors, Virus - metabolism</subject><subject>Respiratory diseases</subject><subject>Sarbecovirus</subject><subject>SARS-CoV-2</subject><subject>Severe Acute Respiratory Syndrome - immunology</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Severe acute respiratory syndrome-related coronavirus - immunology</subject><subject>Somatic hypermutation</subject><subject>Somatic Hypermutation, Immunoglobulin</subject><subject>Spike Glycoprotein, Coronavirus - chemistry</subject><subject>Spike Glycoprotein, Coronavirus - immunology</subject><subject>Spike Glycoprotein, Coronavirus - metabolism</subject><subject>Spike protein</subject><subject>Vaccines</subject><subject>Viral diseases</subject><subject>Viruses</subject><subject>Young 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neutralization of SARS-related viruses by human monoclonal antibodies</title><author>Wec, Anna Z ; Wrapp, Daniel ; Herbert, Andrew S ; Maurer, Daniel P ; Haslwanter, Denise ; Sakharkar, Mrunal ; Jangra, Rohit K ; Dieterle, M Eugenia ; Lilov, Asparouh ; Huang, Deli ; Tse, Longping V ; Johnson, Nicole V ; Hsieh, Ching-Lin ; Wang, Nianshuang ; Nett, Juergen H ; Champney, Elizabeth ; Burnina, Irina ; Brown, Michael ; Lin, Shu ; Sinclair, Melanie ; Johnson, Carl ; Pudi, Sarat ; Bortz, 3rd, Robert ; Wirchnianski, Ariel S ; Laudermilch, Ethan ; Florez, Catalina ; Fels, J Maximilian ; O'Brien, Cecilia M ; Graham, Barney S ; Nemazee, David ; Burton, Dennis R ; Baric, Ralph S ; Voss, James E ; Chandran, Kartik ; Dye, John M ; McLellan, Jason S ; Walker, Laura 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Hypermutation, Immunoglobulin</topic><topic>Spike Glycoprotein, Coronavirus - chemistry</topic><topic>Spike Glycoprotein, Coronavirus - immunology</topic><topic>Spike Glycoprotein, Coronavirus - metabolism</topic><topic>Spike protein</topic><topic>Vaccines</topic><topic>Viral diseases</topic><topic>Viruses</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wec, Anna Z</creatorcontrib><creatorcontrib>Wrapp, Daniel</creatorcontrib><creatorcontrib>Herbert, Andrew S</creatorcontrib><creatorcontrib>Maurer, Daniel P</creatorcontrib><creatorcontrib>Haslwanter, Denise</creatorcontrib><creatorcontrib>Sakharkar, Mrunal</creatorcontrib><creatorcontrib>Jangra, Rohit K</creatorcontrib><creatorcontrib>Dieterle, M Eugenia</creatorcontrib><creatorcontrib>Lilov, Asparouh</creatorcontrib><creatorcontrib>Huang, Deli</creatorcontrib><creatorcontrib>Tse, Longping V</creatorcontrib><creatorcontrib>Johnson, Nicole 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S</creatorcontrib><creatorcontrib>Voss, James E</creatorcontrib><creatorcontrib>Chandran, Kartik</creatorcontrib><creatorcontrib>Dye, John M</creatorcontrib><creatorcontrib>McLellan, Jason S</creatorcontrib><creatorcontrib>Walker, Laura M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications 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Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wec, Anna Z</au><au>Wrapp, Daniel</au><au>Herbert, Andrew S</au><au>Maurer, Daniel P</au><au>Haslwanter, Denise</au><au>Sakharkar, Mrunal</au><au>Jangra, Rohit K</au><au>Dieterle, M Eugenia</au><au>Lilov, Asparouh</au><au>Huang, Deli</au><au>Tse, Longping V</au><au>Johnson, Nicole V</au><au>Hsieh, Ching-Lin</au><au>Wang, Nianshuang</au><au>Nett, Juergen H</au><au>Champney, Elizabeth</au><au>Burnina, Irina</au><au>Brown, Michael</au><au>Lin, Shu</au><au>Sinclair, Melanie</au><au>Johnson, Carl</au><au>Pudi, Sarat</au><au>Bortz, 3rd, Robert</au><au>Wirchnianski, Ariel S</au><au>Laudermilch, Ethan</au><au>Florez, Catalina</au><au>Fels, J Maximilian</au><au>O'Brien, Cecilia M</au><au>Graham, Barney S</au><au>Nemazee, David</au><au>Burton, Dennis R</au><au>Baric, Ralph S</au><au>Voss, James E</au><au>Chandran, Kartik</au><au>Dye, John M</au><au>McLellan, Jason S</au><au>Walker, Laura M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Broad neutralization of SARS-related viruses by human monoclonal antibodies</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2020-08-07</date><risdate>2020</risdate><volume>369</volume><issue>6504</issue><spage>731</spage><epage>736</epage><pages>731-736</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><abstract>Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.</abstract><cop>United States</cop><pub>The American Association for the Advancement of Science</pub><pmid>32540900</pmid><doi>10.1126/science.abc7424</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-0883-5016</orcidid><orcidid>https://orcid.org/0000-0002-4769-6311</orcidid><orcidid>https://orcid.org/0000-0003-4351-125X</orcidid><orcidid>https://orcid.org/0000-0002-3953-8954</orcidid><orcidid>https://orcid.org/0000-0002-0538-9647</orcidid><orcidid>https://orcid.org/0000-0002-7569-011X</orcidid><orcidid>https://orcid.org/0000-0002-2134-2152</orcidid><orcidid>https://orcid.org/0000-0002-4698-7264</orcidid><orcidid>https://orcid.org/0000-0001-7582-8396</orcidid><orcidid>https://orcid.org/0000-0002-1410-683X</orcidid><orcidid>https://orcid.org/0000-0003-2727-0468</orcidid><orcidid>https://orcid.org/0000-0003-3400-7203</orcidid><orcidid>https://orcid.org/0000-0002-4777-1596</orcidid><orcidid>https://orcid.org/0000-0002-0407-861X</orcidid><orcidid>https://orcid.org/0000-0001-7160-0220</orcidid><orcidid>https://orcid.org/0000-0001-8112-0853</orcidid><orcidid>https://orcid.org/0000-0003-1751-2152</orcidid><orcidid>https://orcid.org/0000-0001-7704-3197</orcidid><orcidid>https://orcid.org/0000-0003-1455-9318</orcidid><orcidid>https://orcid.org/0000-0003-3292-2117</orcidid><orcidid>https://orcid.org/0000-0001-6711-9864</orcidid><orcidid>https://orcid.org/0000-0002-3119-0869</orcidid><orcidid>https://orcid.org/0000-0002-5257-7253</orcidid><orcidid>https://orcid.org/0000-0003-4697-7928</orcidid><orcidid>https://orcid.org/0000-0001-6827-8701</orcidid><orcidid>https://orcid.org/0000-0003-3991-542X</orcidid><orcidid>https://orcid.org/0000-0002-6989-639X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2020-08, Vol.369 (6504), p.731-736 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7299279 |
| source | MEDLINE; American Association for the Advancement of Science |
| subjects | ACE2 Adult Aged Angiotensin Angiotensin-Converting Enzyme 2 Antibodies Antibodies, Monoclonal - immunology Antibodies, Viral - immunology Antibody Affinity B-Lymphocyte Subsets - immunology Betacoronavirus - immunology Binding Binding Sites Broadly Neutralizing Antibodies - immunology Coronaviridae Coronaviruses COVID-19 Cross Reactions Epitopes Female Humans Immunologic Memory Immunological memory Immunology Lymphocytes B Male Memory Memory cells Microbio Middle Aged Monoclonal antibodies Neutralization Neutralization Tests Neutralizing Peptidyl-dipeptidase A Peptidyl-Dipeptidase A - chemistry Peptidyl-Dipeptidase A - metabolism Protein Domains Proteins Receptors Receptors, Coronavirus Receptors, Virus - chemistry Receptors, Virus - metabolism Respiratory diseases Sarbecovirus SARS-CoV-2 Severe Acute Respiratory Syndrome - immunology Severe acute respiratory syndrome coronavirus 2 Severe acute respiratory syndrome-related coronavirus - immunology Somatic hypermutation Somatic Hypermutation, Immunoglobulin Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - immunology Spike Glycoprotein, Coronavirus - metabolism Spike protein Vaccines Viral diseases Viruses Young Adult |
| title | Broad neutralization of SARS-related viruses by human monoclonal antibodies |
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