Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
Identifieur interne : 000020 ( Pmc/Corpus ); précédent : 000019; suivant : 000021Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
Auteurs : Davide Corti ; Jincun Zhao ; Mattia Pedotti ; Luca Simonelli ; Sudhakar Agnihothram ; Craig Fett ; Blanca Fernandez-Rodriguez ; Mathilde Foglierini ; Gloria Agatic ; Fabrizia Vanzetta ; Robin Gopal ; Christopher J. Langrish ; Nicholas A. Barrett ; Federica Sallusto ; Ralph S. Baric ; Luca Varani ; Maria Zambon ; Stanley Perlman ; Antonio LanzavecchiaSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2015.
Abstract
Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe respiratory disease with a high mortality rate. There is no licensed vaccine or antiviral for MERS. Here we isolated for the first time, to our knowledge, a potent MERS-CoV–neutralizing antibody from memory B cells of an infected individual. This antibody binds to a novel site on the viral Spike protein, neutralizes by interfering with the binding to the cellular receptor CD26, and is highly effective both in prophylaxis and in therapy in a relevant mouse model. This antibody can be developed for prophylaxis, for postexposure prophylaxis, or for the treatment of severe MERS-CoV infections.
Url:
DOI: 10.1073/pnas.1510199112
PubMed: 26216974
PubMed Central: 4547275
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PMC:4547275Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus</title><author><name sortKey="Corti, Davide" sort="Corti, Davide" uniqKey="Corti D" first="Davide" last="Corti">Davide Corti</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>Humabs BioMed SA</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name><affiliation><nlm:aff id="aff3">Department of Microbiology,<institution>University of Iowa</institution>, Iowa City,<addr-line>IA</addr-line> 52240;</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease,<institution>The First Affiliated Hospital of Guangzhou Medical University</institution>, Guangzhou 510120,<country>China</country>;</nlm:aff></affiliation></author><author><name sortKey="Pedotti, Mattia" sort="Pedotti, Mattia" uniqKey="Pedotti M" first="Mattia" last="Pedotti">Mattia Pedotti</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Simonelli, Luca" sort="Simonelli, Luca" uniqKey="Simonelli L" first="Luca" last="Simonelli">Luca Simonelli</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name><affiliation><nlm:aff id="aff5">Department of Microbiology and Immunology,<institution>University of North Carolina at Chapel Hill</institution>, Chapel Hill,<addr-line>NC</addr-line> 27599;</nlm:aff></affiliation></author><author><name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name><affiliation><nlm:aff id="aff5">Department of Microbiology and Immunology,<institution>University of North Carolina at Chapel Hill</institution>, Chapel Hill,<addr-line>NC</addr-line> 27599;</nlm:aff></affiliation></author><author><name sortKey="Fernandez Rodriguez, Blanca" sort="Fernandez Rodriguez, Blanca" uniqKey="Fernandez Rodriguez B" first="Blanca" last="Fernandez-Rodriguez">Blanca Fernandez-Rodriguez</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Foglierini, Mathilde" sort="Foglierini, Mathilde" uniqKey="Foglierini M" first="Mathilde" last="Foglierini">Mathilde Foglierini</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Agatic, Gloria" sort="Agatic, Gloria" uniqKey="Agatic G" first="Gloria" last="Agatic">Gloria Agatic</name><affiliation><nlm:aff id="aff2"><institution>Humabs BioMed SA</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Vanzetta, Fabrizia" sort="Vanzetta, Fabrizia" uniqKey="Vanzetta F" first="Fabrizia" last="Vanzetta">Fabrizia Vanzetta</name><affiliation><nlm:aff id="aff2"><institution>Humabs BioMed SA</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Gopal, Robin" sort="Gopal, Robin" uniqKey="Gopal R" first="Robin" last="Gopal">Robin Gopal</name><affiliation><nlm:aff id="aff6">Microbiology Services Colindale,<institution>Public Health England</institution>, London NW9 5HT,<country>United Kingdom</country>;</nlm:aff></affiliation></author><author><name sortKey="Langrish, Christopher J" sort="Langrish, Christopher J" uniqKey="Langrish C" first="Christopher J." last="Langrish">Christopher J. Langrish</name><affiliation><nlm:aff id="aff7"><institution>Guy’s and St. Thomas’ National Health Service Foundation Trust</institution>, London SE1 7EH,<country>United Kingdom</country>;</nlm:aff></affiliation></author><author><name sortKey="Barrett, Nicholas A" sort="Barrett, Nicholas A" uniqKey="Barrett N" first="Nicholas A" last="Barrett">Nicholas A. Barrett</name><affiliation><nlm:aff id="aff7"><institution>Guy’s and St. Thomas’ National Health Service Foundation Trust</institution>, London SE1 7EH,<country>United Kingdom</country>;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8"><institution>King’s College London, Strand</institution>, London WC2R 2LS,<country>United Kingdom</country>;</nlm:aff></affiliation></author><author><name sortKey="Sallusto, Federica" sort="Sallusto, Federica" uniqKey="Sallusto F" first="Federica" last="Sallusto">Federica Sallusto</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation><nlm:aff id="aff5">Department of Microbiology and Immunology,<institution>University of North Carolina at Chapel Hill</institution>, Chapel Hill,<addr-line>NC</addr-line> 27599;</nlm:aff></affiliation><affiliation><nlm:aff id="aff9">Department of Epidemiology,<institution>University of North Carolina at Chapel Hill</institution>, Chapel Hill,<addr-line>NC</addr-line> 27599;</nlm:aff></affiliation></author><author><name sortKey="Varani, Luca" sort="Varani, Luca" uniqKey="Varani L" first="Luca" last="Varani">Luca Varani</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Zambon, Maria" sort="Zambon, Maria" uniqKey="Zambon M" first="Maria" last="Zambon">Maria Zambon</name><affiliation><nlm:aff id="aff6">Microbiology Services Colindale,<institution>Public Health England</institution>, London NW9 5HT,<country>United Kingdom</country>;</nlm:aff></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation><nlm:aff id="aff3">Department of Microbiology,<institution>University of Iowa</institution>, Iowa City,<addr-line>IA</addr-line> 52240;</nlm:aff></affiliation></author><author><name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation><affiliation><nlm:aff id="aff10">Institute of Microbiology,<institution>Eidgenössische Technische Hochschule Zurich</institution>, 8093 Zurich,<country>Switzerland</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26216974</idno><idno type="pmc">4547275</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547275</idno><idno type="RBID">PMC:4547275</idno><idno type="doi">10.1073/pnas.1510199112</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000020</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000020</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus</title><author><name sortKey="Corti, Davide" sort="Corti, Davide" uniqKey="Corti D" first="Davide" last="Corti">Davide Corti</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>Humabs BioMed SA</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name><affiliation><nlm:aff id="aff3">Department of Microbiology,<institution>University of Iowa</institution>, Iowa City,<addr-line>IA</addr-line> 52240;</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease,<institution>The First Affiliated Hospital of Guangzhou Medical University</institution>, Guangzhou 510120,<country>China</country>;</nlm:aff></affiliation></author><author><name sortKey="Pedotti, Mattia" sort="Pedotti, Mattia" uniqKey="Pedotti M" first="Mattia" last="Pedotti">Mattia Pedotti</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Simonelli, Luca" sort="Simonelli, Luca" uniqKey="Simonelli L" first="Luca" last="Simonelli">Luca Simonelli</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name><affiliation><nlm:aff id="aff5">Department of Microbiology and Immunology,<institution>University of North Carolina at Chapel Hill</institution>, Chapel Hill,<addr-line>NC</addr-line> 27599;</nlm:aff></affiliation></author><author><name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name><affiliation><nlm:aff id="aff5">Department of Microbiology and Immunology,<institution>University of North Carolina at Chapel Hill</institution>, Chapel Hill,<addr-line>NC</addr-line> 27599;</nlm:aff></affiliation></author><author><name sortKey="Fernandez Rodriguez, Blanca" sort="Fernandez Rodriguez, Blanca" uniqKey="Fernandez Rodriguez B" first="Blanca" last="Fernandez-Rodriguez">Blanca Fernandez-Rodriguez</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Foglierini, Mathilde" sort="Foglierini, Mathilde" uniqKey="Foglierini M" first="Mathilde" last="Foglierini">Mathilde Foglierini</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Agatic, Gloria" sort="Agatic, Gloria" uniqKey="Agatic G" first="Gloria" last="Agatic">Gloria Agatic</name><affiliation><nlm:aff id="aff2"><institution>Humabs BioMed SA</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Vanzetta, Fabrizia" sort="Vanzetta, Fabrizia" uniqKey="Vanzetta F" first="Fabrizia" last="Vanzetta">Fabrizia Vanzetta</name><affiliation><nlm:aff id="aff2"><institution>Humabs BioMed SA</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Gopal, Robin" sort="Gopal, Robin" uniqKey="Gopal R" first="Robin" last="Gopal">Robin Gopal</name><affiliation><nlm:aff id="aff6">Microbiology Services Colindale,<institution>Public Health England</institution>, London NW9 5HT,<country>United Kingdom</country>;</nlm:aff></affiliation></author><author><name sortKey="Langrish, Christopher J" sort="Langrish, Christopher J" uniqKey="Langrish C" first="Christopher J." last="Langrish">Christopher J. Langrish</name><affiliation><nlm:aff id="aff7"><institution>Guy’s and St. Thomas’ National Health Service Foundation Trust</institution>, London SE1 7EH,<country>United Kingdom</country>;</nlm:aff></affiliation></author><author><name sortKey="Barrett, Nicholas A" sort="Barrett, Nicholas A" uniqKey="Barrett N" first="Nicholas A" last="Barrett">Nicholas A. Barrett</name><affiliation><nlm:aff id="aff7"><institution>Guy’s and St. Thomas’ National Health Service Foundation Trust</institution>, London SE1 7EH,<country>United Kingdom</country>;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8"><institution>King’s College London, Strand</institution>, London WC2R 2LS,<country>United Kingdom</country>;</nlm:aff></affiliation></author><author><name sortKey="Sallusto, Federica" sort="Sallusto, Federica" uniqKey="Sallusto F" first="Federica" last="Sallusto">Federica Sallusto</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation><nlm:aff id="aff5">Department of Microbiology and Immunology,<institution>University of North Carolina at Chapel Hill</institution>, Chapel Hill,<addr-line>NC</addr-line> 27599;</nlm:aff></affiliation><affiliation><nlm:aff id="aff9">Department of Epidemiology,<institution>University of North Carolina at Chapel Hill</institution>, Chapel Hill,<addr-line>NC</addr-line> 27599;</nlm:aff></affiliation></author><author><name sortKey="Varani, Luca" sort="Varani, Luca" uniqKey="Varani L" first="Luca" last="Varani">Luca Varani</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation></author><author><name sortKey="Zambon, Maria" sort="Zambon, Maria" uniqKey="Zambon M" first="Maria" last="Zambon">Maria Zambon</name><affiliation><nlm:aff id="aff6">Microbiology Services Colindale,<institution>Public Health England</institution>, London NW9 5HT,<country>United Kingdom</country>;</nlm:aff></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation><nlm:aff id="aff3">Department of Microbiology,<institution>University of Iowa</institution>, Iowa City,<addr-line>IA</addr-line> 52240;</nlm:aff></affiliation></author><author><name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name><affiliation><nlm:aff id="aff1">Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</nlm:aff></affiliation><affiliation><nlm:aff id="aff10">Institute of Microbiology,<institution>Eidgenössische Technische Hochschule Zurich</institution>, 8093 Zurich,<country>Switzerland</country></nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe respiratory disease with a high mortality rate. There is no licensed vaccine or antiviral for MERS. Here we isolated for the first time, to our knowledge, a potent MERS-CoV–neutralizing antibody from memory B cells of an infected individual. This antibody binds to a novel site on the viral Spike protein, neutralizes by interfering with the binding to the cellular receptor CD26, and is highly effective both in prophylaxis and in therapy in a relevant mouse model. This antibody can be developed for prophylaxis, for postexposure prophylaxis, or for the treatment of severe MERS-CoV infections.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="iso-abbrev">Proc. Natl. Acad. Sci. U.S.A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26216974</article-id><article-id pub-id-type="pmc">4547275</article-id><article-id pub-id-type="publisher-id">201510199</article-id><article-id pub-id-type="doi">10.1073/pnas.1510199112</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Microbiology</subject></subj-group></subj-group><series-title>From the Cover</series-title></article-categories><title-group><article-title>Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus</article-title><alt-title alt-title-type="short">Anti-MERS coronavirus human neutralizing antibody</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Corti</surname><given-names>Davide</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Jincun</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pedotti</surname><given-names>Mattia</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Simonelli</surname><given-names>Luca</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Agnihothram</surname><given-names>Sudhakar</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fett</surname><given-names>Craig</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fernandez-Rodriguez</surname><given-names>Blanca</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Foglierini</surname><given-names>Mathilde</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Agatic</surname><given-names>Gloria</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vanzetta</surname><given-names>Fabrizia</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gopal</surname><given-names>Robin</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Langrish</surname><given-names>Christopher J.</given-names></name><xref ref-type="aff" rid="aff7"><sup>g</sup></xref></contrib><contrib contrib-type="author"><name><surname>Barrett</surname><given-names>Nicholas A</given-names></name><xref ref-type="aff" rid="aff7"><sup>g</sup></xref><xref ref-type="aff" rid="aff8"><sup>h</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sallusto</surname><given-names>Federica</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Baric</surname><given-names>Ralph S.</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref><xref ref-type="aff" rid="aff9"><sup>i</sup></xref></contrib><contrib contrib-type="author"><name><surname>Varani</surname><given-names>Luca</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zambon</surname><given-names>Maria</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Perlman</surname><given-names>Stanley</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lanzavecchia</surname><given-names>Antonio</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff10"><sup>j</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1"><sup>a</sup>Immune Regulation Unit, Institute for Research in Biomedicine,<institution>Università della Svizzera Italiana</institution>, 6500 Bellinzona,<country>Switzerland</country>;</aff><aff id="aff2"><sup>b</sup><institution>Humabs BioMed SA</institution>, 6500 Bellinzona,<country>Switzerland</country>;</aff><aff id="aff3"><sup>c</sup>Department of Microbiology,<institution>University of Iowa</institution>, Iowa City,<addr-line>IA</addr-line> 52240;</aff><aff id="aff4"><sup>d</sup>State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease,<institution>The First Affiliated Hospital of Guangzhou Medical University</institution>, Guangzhou 510120,<country>China</country>;</aff><aff id="aff5"><sup>e</sup>Department of Microbiology and Immunology,<institution>University of North Carolina at Chapel Hill</institution>, Chapel Hill,<addr-line>NC</addr-line> 27599;</aff><aff id="aff6"><sup>f</sup>Microbiology Services Colindale,<institution>Public Health England</institution>, London NW9 5HT,<country>United Kingdom</country>;</aff><aff id="aff7"><sup>g</sup><institution>Guy’s and St. Thomas’ National Health Service Foundation Trust</institution>, London SE1 7EH,<country>United Kingdom</country>;</aff><aff id="aff8"><sup>h</sup><institution>King’s College London, Strand</institution>, London WC2R 2LS,<country>United Kingdom</country>;</aff><aff id="aff9"><sup>i</sup>Department of Epidemiology,<institution>University of North Carolina at Chapel Hill</institution>, Chapel Hill,<addr-line>NC</addr-line> 27599;</aff><aff id="aff10"><sup>j</sup>Institute of Microbiology,<institution>Eidgenössische Technische Hochschule Zurich</institution>, 8093 Zurich,<country>Switzerland</country></aff></contrib-group><author-notes><corresp id="cor1"><sup>2</sup>To whom correspondence should be addressed. Email: <email>lanzavecchia@irb.usi.ch</email>.</corresp><fn fn-type="edited-by"><p>Edited by Michael B. A. Oldstone, The Scripps Research Institute, La Jolla, CA, and approved June 29, 2015 (received for review May 25, 2015)</p></fn><fn fn-type="con"><p>Author contributions: D.C., J.Z., F.S., R.S.B., L.V., M.Z., S.P., and A.L. designed research; D.C., J.Z., M.P., L.S., S.A., C.F., B.F.-R., G.A., F.V., and R.G. performed research; M.P., L.S., S.A., M.F., C.J.L., N.A.B., and L.V. contributed new reagents/analytic tools; D.C., J.Z., M.P., L.S., S.A., M.F., R.G., and L.V. analyzed data; and D.C., J.Z., F.S., R.S.B., L.V., M.Z., S.P., and A.L. wrote the paper.</p></fn><fn fn-type="equal" id="fn1"><p><sup>1</sup>D.C. and J.Z. contributed equally to this work.</p></fn><fn fn-type="conflict"><p>Conflict of interest statement: A.L. is the scientific founder of Humabs BioMed SA. A.L. holds shares in Humabs BioMed SA. G.A., F.V., and D.C. are employees of Humabs Biomed, a commercial company that commercializes human monoclonal antibodies.</p></fn></author-notes><pub-date pub-type="ppub"><day>18</day><month>8</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>27</day><month>7</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>27</day><month>7</month><year>2015</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>112</volume><issue>33</issue><fpage>10473</fpage><lpage>10478</lpage><permissions><license license-type="open-access"><license-p>Freely available online through the PNAS open access option.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:href="pnas.201510199.pdf"></self-uri><abstract abstract-type="executive-summary"><title>Significance</title><p>Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe respiratory disease with a high mortality rate. There is no licensed vaccine or antiviral for MERS. Here we isolated for the first time, to our knowledge, a potent MERS-CoV–neutralizing antibody from memory B cells of an infected individual. This antibody binds to a novel site on the viral Spike protein, neutralizes by interfering with the binding to the cellular receptor CD26, and is highly effective both in prophylaxis and in therapy in a relevant mouse model. This antibody can be developed for prophylaxis, for postexposure prophylaxis, or for the treatment of severe MERS-CoV infections.</p></abstract><abstract><p>Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV–neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses.</p></abstract><kwd-group><kwd>MERS-CoV</kwd><kwd>neutralizing antibody</kwd><kwd>serotherapy</kwd><kwd>emerging viruses</kwd></kwd-group><counts><page-count count="6"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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