Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak
Antibodies targeting the Ebola virus surface glycoprotein (EBOV GP) are implicated in protection against lethal disease, but the characteristics of the human antibody response to EBOV GP remain poorly understood. We isolated and characterized 349 GP-specific monoclonal antibodies (mAbs) from the per...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2016-03, Vol.351 (6277), p.1078-1083 |
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| creator | Bornholdt, Zachary A. Turner, Hannah L. Murin, Charles D. Li, Wen Sok, Devin Souders, Colby A. Piper, Ashley E. Goff, Arthur Shamblin, Joshua D. Wollen, Suzanne E. Sprague, Thomas R. Fusco, Marnie L. Pommert, Kathleen B. J. Cavacini, Lisa A. Smith, Heidi L. Klempner, Mark Reimann, Keith A. Krauland, Eric Gerngross, Tillman U. Wittrup, Karl D. Saphire, Erica Ollmann Burton, Dennis R. Glass, Pamela J. Ward, Andrew B. Walker, Laura M. |
| description | Antibodies targeting the Ebola virus surface glycoprotein (EBOV GP) are implicated in protection against lethal disease, but the characteristics of the human antibody response to EBOV GP remain poorly understood. We isolated and characterized 349 GP-specific monoclonal antibodies (mAbs) from the peripheral B cells of a convalescent donor who survived the 2014 EBOV Zaire outbreak. Remarkably, 77% of the mAbs neutralize live EBOV, and several mAbs exhibit unprecedented potency. Structures of selected mAbs in complex with GP reveal a site of vulnerability located in the GP stalk region proximal to the viral membrane. Neutralizing antibodies targeting this site show potent therapeutic efficacy against lethal EBOV challenge in mice. The results provide a framework for the design of new EBOV vaccine candidates and immunotherapies. |
| doi_str_mv | 10.1126/science.aad5788 |
| format | Article |
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J. ; Cavacini, Lisa A. ; Smith, Heidi L. ; Klempner, Mark ; Reimann, Keith A. ; Krauland, Eric ; Gerngross, Tillman U. ; Wittrup, Karl D. ; Saphire, Erica Ollmann ; Burton, Dennis R. ; Glass, Pamela J. ; Ward, Andrew B. ; Walker, Laura M.</creator><creatorcontrib>Bornholdt, Zachary A. ; Turner, Hannah L. ; Murin, Charles D. ; Li, Wen ; Sok, Devin ; Souders, Colby A. ; Piper, Ashley E. ; Goff, Arthur ; Shamblin, Joshua D. ; Wollen, Suzanne E. ; Sprague, Thomas R. ; Fusco, Marnie L. ; Pommert, Kathleen B. J. ; Cavacini, Lisa A. ; Smith, Heidi L. ; Klempner, Mark ; Reimann, Keith A. ; Krauland, Eric ; Gerngross, Tillman U. ; Wittrup, Karl D. ; Saphire, Erica Ollmann ; Burton, Dennis R. ; Glass, Pamela J. ; Ward, Andrew B. ; Walker, Laura M.</creatorcontrib><description>Antibodies targeting the Ebola virus surface glycoprotein (EBOV GP) are implicated in protection against lethal disease, but the characteristics of the human antibody response to EBOV GP remain poorly understood. We isolated and characterized 349 GP-specific monoclonal antibodies (mAbs) from the peripheral B cells of a convalescent donor who survived the 2014 EBOV Zaire outbreak. Remarkably, 77% of the mAbs neutralize live EBOV, and several mAbs exhibit unprecedented potency. Structures of selected mAbs in complex with GP reveal a site of vulnerability located in the GP stalk region proximal to the viral membrane. Neutralizing antibodies targeting this site show potent therapeutic efficacy against lethal EBOV challenge in mice. The results provide a framework for the design of new EBOV vaccine candidates and immunotherapies.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aad5788</identifier><identifier>PMID: 26912366</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Animals ; Antibodies, Monoclonal - chemistry ; Antibodies, Monoclonal - isolation & purification ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Neutralizing - chemistry ; Antibodies, Neutralizing - isolation & purification ; Antibodies, Neutralizing - therapeutic use ; Antibodies, Viral - chemistry ; Antibodies, Viral - isolation & purification ; Antibodies, Viral - therapeutic use ; Antibody Formation ; Antigen-Antibody Complex - chemistry ; Democratic Republic of the Congo - epidemiology ; Disease Outbreaks ; Ebola Vaccines - immunology ; Ebola Vaccines - therapeutic use ; Ebola virus ; Ebolavirus - immunology ; Hemorrhagic Fever, Ebola - epidemiology ; Hemorrhagic Fever, Ebola - immunology ; Hemorrhagic Fever, Ebola - therapy ; Humans ; Immunization, Passive ; Mice ; Monoclonal antibodies ; Structural Analysis (Linguistics) ; Structural Analysis (Science) ; Survivors ; Tissue Donors ; Viral Envelope Proteins - chemistry ; Viral Envelope Proteins - immunology ; Virion - immunology</subject><ispartof>Science (American Association for the Advancement of Science), 2016-03, Vol.351 (6277), p.1078-1083</ispartof><rights>Copyright © 2016 American Association for the Advancement of Science</rights><rights>Copyright © 2016, American Association for the Advancement of Science.</rights><rights>Copyright © 2016, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c625t-7ac06e2590c35f03ba75d46fede23ef156373429222f5c1d4108da07e5740f6f3</citedby><cites>FETCH-LOGICAL-c625t-7ac06e2590c35f03ba75d46fede23ef156373429222f5c1d4108da07e5740f6f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24742530$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24742530$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26912366$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bornholdt, Zachary A.</creatorcontrib><creatorcontrib>Turner, Hannah L.</creatorcontrib><creatorcontrib>Murin, Charles D.</creatorcontrib><creatorcontrib>Li, Wen</creatorcontrib><creatorcontrib>Sok, Devin</creatorcontrib><creatorcontrib>Souders, Colby A.</creatorcontrib><creatorcontrib>Piper, Ashley E.</creatorcontrib><creatorcontrib>Goff, Arthur</creatorcontrib><creatorcontrib>Shamblin, Joshua D.</creatorcontrib><creatorcontrib>Wollen, Suzanne E.</creatorcontrib><creatorcontrib>Sprague, Thomas R.</creatorcontrib><creatorcontrib>Fusco, Marnie L.</creatorcontrib><creatorcontrib>Pommert, Kathleen B. J.</creatorcontrib><creatorcontrib>Cavacini, Lisa A.</creatorcontrib><creatorcontrib>Smith, Heidi L.</creatorcontrib><creatorcontrib>Klempner, Mark</creatorcontrib><creatorcontrib>Reimann, Keith A.</creatorcontrib><creatorcontrib>Krauland, Eric</creatorcontrib><creatorcontrib>Gerngross, Tillman U.</creatorcontrib><creatorcontrib>Wittrup, Karl D.</creatorcontrib><creatorcontrib>Saphire, Erica Ollmann</creatorcontrib><creatorcontrib>Burton, Dennis R.</creatorcontrib><creatorcontrib>Glass, Pamela J.</creatorcontrib><creatorcontrib>Ward, Andrew B.</creatorcontrib><creatorcontrib>Walker, Laura M.</creatorcontrib><title>Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Antibodies targeting the Ebola virus surface glycoprotein (EBOV GP) are implicated in protection against lethal disease, but the characteristics of the human antibody response to EBOV GP remain poorly understood. We isolated and characterized 349 GP-specific monoclonal antibodies (mAbs) from the peripheral B cells of a convalescent donor who survived the 2014 EBOV Zaire outbreak. Remarkably, 77% of the mAbs neutralize live EBOV, and several mAbs exhibit unprecedented potency. Structures of selected mAbs in complex with GP reveal a site of vulnerability located in the GP stalk region proximal to the viral membrane. Neutralizing antibodies targeting this site show potent therapeutic efficacy against lethal EBOV challenge in mice. The results provide a framework for the design of new EBOV vaccine candidates and immunotherapies.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibodies, Monoclonal - isolation & purification</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Neutralizing - chemistry</subject><subject>Antibodies, Neutralizing - isolation & purification</subject><subject>Antibodies, Neutralizing - therapeutic use</subject><subject>Antibodies, Viral - chemistry</subject><subject>Antibodies, Viral - isolation & purification</subject><subject>Antibodies, Viral - therapeutic use</subject><subject>Antibody Formation</subject><subject>Antigen-Antibody Complex - chemistry</subject><subject>Democratic Republic of the Congo - epidemiology</subject><subject>Disease Outbreaks</subject><subject>Ebola Vaccines - immunology</subject><subject>Ebola Vaccines - therapeutic use</subject><subject>Ebola virus</subject><subject>Ebolavirus - immunology</subject><subject>Hemorrhagic Fever, Ebola - epidemiology</subject><subject>Hemorrhagic Fever, Ebola - immunology</subject><subject>Hemorrhagic Fever, Ebola - therapy</subject><subject>Humans</subject><subject>Immunization, Passive</subject><subject>Mice</subject><subject>Monoclonal antibodies</subject><subject>Structural Analysis (Linguistics)</subject><subject>Structural Analysis (Science)</subject><subject>Survivors</subject><subject>Tissue Donors</subject><subject>Viral Envelope Proteins - chemistry</subject><subject>Viral Envelope Proteins - immunology</subject><subject>Virion - immunology</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc9rFDEcxYNY7Fo9e1ICXrxM-83vmYsgpWqh4EVvQshkkjbrbLImmQX96027a209fQ_v8x7fx0PoFYFTQqg8Kza4aN2pMZNQff8ErQgMohsosKdoBcBk14MSx-h5KWuApg3sGTqmciCUSblC3y9Lmk0NKeLk8TZVFyuObqnZzOF3iNfYxBrGNAVXsM9pgw0uS96FXcq3jnrjMAXC8cXYcvAu5KXgtNQxO_PjBTryZi7u5eGeoG8fL76ef-6uvny6PP9w1VlJRe2UsSAdFQNYJjyw0Sgxcend5ChzngjJFON0oJR6YcnECfSTAeWE4uClZyfo_T53u4wbN9nWob2vtzlsTP6lkwn6sRLDjb5OO80HACVZC3h3CMjp5-JK1ZtQrJtnE11aiiZKQa8E6XlD3_6HrtOSY6t3R3EQ_dA36mxP2ZxKyc7fP0NA3y6nD8vpw3LN8eZhh3v-71QNeL0H1qWm_E_nilPBgP0BZICg6g</recordid><startdate>20160304</startdate><enddate>20160304</enddate><creator>Bornholdt, Zachary A.</creator><creator>Turner, Hannah L.</creator><creator>Murin, Charles D.</creator><creator>Li, Wen</creator><creator>Sok, Devin</creator><creator>Souders, Colby A.</creator><creator>Piper, Ashley E.</creator><creator>Goff, Arthur</creator><creator>Shamblin, Joshua D.</creator><creator>Wollen, Suzanne E.</creator><creator>Sprague, Thomas R.</creator><creator>Fusco, Marnie L.</creator><creator>Pommert, Kathleen B. 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We isolated and characterized 349 GP-specific monoclonal antibodies (mAbs) from the peripheral B cells of a convalescent donor who survived the 2014 EBOV Zaire outbreak. Remarkably, 77% of the mAbs neutralize live EBOV, and several mAbs exhibit unprecedented potency. Structures of selected mAbs in complex with GP reveal a site of vulnerability located in the GP stalk region proximal to the viral membrane. Neutralizing antibodies targeting this site show potent therapeutic efficacy against lethal EBOV challenge in mice. The results provide a framework for the design of new EBOV vaccine candidates and immunotherapies.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>26912366</pmid><doi>10.1126/science.aad5788</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2016-03, Vol.351 (6277), p.1078-1083 |
| issn | 0036-8075 1095-9203 |
| language | eng |
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| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Animals Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - isolation & purification Antibodies, Monoclonal - therapeutic use Antibodies, Neutralizing - chemistry Antibodies, Neutralizing - isolation & purification Antibodies, Neutralizing - therapeutic use Antibodies, Viral - chemistry Antibodies, Viral - isolation & purification Antibodies, Viral - therapeutic use Antibody Formation Antigen-Antibody Complex - chemistry Democratic Republic of the Congo - epidemiology Disease Outbreaks Ebola Vaccines - immunology Ebola Vaccines - therapeutic use Ebola virus Ebolavirus - immunology Hemorrhagic Fever, Ebola - epidemiology Hemorrhagic Fever, Ebola - immunology Hemorrhagic Fever, Ebola - therapy Humans Immunization, Passive Mice Monoclonal antibodies Structural Analysis (Linguistics) Structural Analysis (Science) Survivors Tissue Donors Viral Envelope Proteins - chemistry Viral Envelope Proteins - immunology Virion - immunology |
| title | Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak |
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