Development and Characterization of a Severe Acute Respiratory Syndrome—Associated Coronavirus—Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice
Identifieur interne : 001361 ( Pmc/Checkpoint ); précédent : 001360; suivant : 001362Development and Characterization of a Severe Acute Respiratory Syndrome—Associated Coronavirus—Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice
Auteurs : Thomas C. Greenough ; Gregory J. Babcock ; Anjeanette Roberts [États-Unis] ; Hector J. Hernandez ; William D. Thomas ; Jennifer A. Coccia ; Robert F. Graziano [États-Unis] ; Mohan Srinivasan [États-Unis] ; Israel Lowy [États-Unis] ; Robert W. Finberg ; Kanta Subbarao [États-Unis] ; Leatrice Vogel [États-Unis] ; Mohan Somasundaran ; Katherine Luzuriaga ; John L. Sullivan ; Donna M. AmbrosinoSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2005.
Abstract
Url:
DOI: 10.1086/427242
PubMed: 15655773
PubMed Central: 7110081
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Development and Characterization of a Severe Acute Respiratory Syndrome—Associated Coronavirus—Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice</title><author><name sortKey="Greenough, Thomas C" sort="Greenough, Thomas C" uniqKey="Greenough T" first="Thomas C." last="Greenough">Thomas C. Greenough</name><affiliation><nlm:aff id="aff1"><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></nlm:aff></affiliation></author><author><name sortKey="Babcock, Gregory J" sort="Babcock, Gregory J" uniqKey="Babcock G" first="Gregory J." last="Babcock">Gregory J. Babcock</name><affiliation><nlm:aff id="aff2"><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></nlm:aff></affiliation></author><author><name sortKey="Roberts, Anjeanette" sort="Roberts, Anjeanette" uniqKey="Roberts A" first="Anjeanette" last="Roberts">Anjeanette Roberts</name><affiliation wicri:level="2"><nlm:aff id="aff3"><institution>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Bethesda, Maryland</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Hernandez, Hector J" sort="Hernandez, Hector J" uniqKey="Hernandez H" first="Hector J." last="Hernandez">Hector J. Hernandez</name><affiliation><nlm:aff id="aff2"><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></nlm:aff></affiliation></author><author><name sortKey="Thomas, William D" sort="Thomas, William D" uniqKey="Thomas W" first="William D." last="Thomas">William D. Thomas</name><affiliation><nlm:aff id="aff2"><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></nlm:aff></affiliation></author><author><name sortKey="Coccia, Jennifer A" sort="Coccia, Jennifer A" uniqKey="Coccia J" first="Jennifer A." last="Coccia">Jennifer A. Coccia</name><affiliation><nlm:aff id="aff2"><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></nlm:aff></affiliation></author><author><name sortKey="Graziano, Robert F" sort="Graziano, Robert F" uniqKey="Graziano R" first="Robert F." last="Graziano">Robert F. Graziano</name><affiliation wicri:level="2"><nlm:aff id="aff4"><institution>Medarex, Inc.</institution>,<addr-line>Bloomsbury, New Jersey</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Bloomsbury</wicri:cityArea></affiliation></author><author><name sortKey="Srinivasan, Mohan" sort="Srinivasan, Mohan" uniqKey="Srinivasan M" first="Mohan" last="Srinivasan">Mohan Srinivasan</name><affiliation wicri:level="2"><nlm:aff id="aff4"><institution>Medarex, Inc.</institution>,<addr-line>Bloomsbury, New Jersey</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Bloomsbury</wicri:cityArea></affiliation></author><author><name sortKey="Lowy, Israel" sort="Lowy, Israel" uniqKey="Lowy I" first="Israel" last="Lowy">Israel Lowy</name><affiliation wicri:level="2"><nlm:aff id="aff4"><institution>Medarex, Inc.</institution>,<addr-line>Bloomsbury, New Jersey</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Bloomsbury</wicri:cityArea></affiliation></author><author><name sortKey="Finberg, Robert W" sort="Finberg, Robert W" uniqKey="Finberg R" first="Robert W" last="Finberg">Robert W. Finberg</name><affiliation><nlm:aff id="aff1"><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></nlm:aff></affiliation></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><affiliation wicri:level="2"><nlm:aff id="aff3"><institution>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Bethesda, Maryland</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name><affiliation wicri:level="2"><nlm:aff id="aff3"><institution>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Bethesda, Maryland</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Somasundaran, Mohan" sort="Somasundaran, Mohan" uniqKey="Somasundaran M" first="Mohan" last="Somasundaran">Mohan Somasundaran</name><affiliation><nlm:aff id="aff1"><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></nlm:aff></affiliation></author><author><name sortKey="Luzuriaga, Katherine" sort="Luzuriaga, Katherine" uniqKey="Luzuriaga K" first="Katherine" last="Luzuriaga">Katherine Luzuriaga</name><affiliation><nlm:aff id="aff1"><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></nlm:aff></affiliation></author><author><name sortKey="Sullivan, John L" sort="Sullivan, John L" uniqKey="Sullivan J" first="John L." last="Sullivan">John L. Sullivan</name><affiliation><nlm:aff id="aff1"><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ambrosino, Donna M" sort="Ambrosino, Donna M" uniqKey="Ambrosino D" first="Donna M." last="Ambrosino">Donna M. Ambrosino</name><affiliation><nlm:aff id="aff2"><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">15655773</idno><idno type="pmc">7110081</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110081</idno><idno type="RBID">PMC:7110081</idno><idno type="doi">10.1086/427242</idno><date when="2005">2005</date><idno type="wicri:Area/Pmc/Corpus">001166</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001166</idno><idno type="wicri:Area/Pmc/Curation">001166</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001166</idno><idno type="wicri:Area/Pmc/Checkpoint">001361</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001361</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Development and Characterization of a Severe Acute Respiratory Syndrome—Associated Coronavirus—Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice</title><author><name sortKey="Greenough, Thomas C" sort="Greenough, Thomas C" uniqKey="Greenough T" first="Thomas C." last="Greenough">Thomas C. Greenough</name><affiliation><nlm:aff id="aff1"><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></nlm:aff></affiliation></author><author><name sortKey="Babcock, Gregory J" sort="Babcock, Gregory J" uniqKey="Babcock G" first="Gregory J." last="Babcock">Gregory J. Babcock</name><affiliation><nlm:aff id="aff2"><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></nlm:aff></affiliation></author><author><name sortKey="Roberts, Anjeanette" sort="Roberts, Anjeanette" uniqKey="Roberts A" first="Anjeanette" last="Roberts">Anjeanette Roberts</name><affiliation wicri:level="2"><nlm:aff id="aff3"><institution>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Bethesda, Maryland</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Hernandez, Hector J" sort="Hernandez, Hector J" uniqKey="Hernandez H" first="Hector J." last="Hernandez">Hector J. Hernandez</name><affiliation><nlm:aff id="aff2"><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></nlm:aff></affiliation></author><author><name sortKey="Thomas, William D" sort="Thomas, William D" uniqKey="Thomas W" first="William D." last="Thomas">William D. Thomas</name><affiliation><nlm:aff id="aff2"><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></nlm:aff></affiliation></author><author><name sortKey="Coccia, Jennifer A" sort="Coccia, Jennifer A" uniqKey="Coccia J" first="Jennifer A." last="Coccia">Jennifer A. Coccia</name><affiliation><nlm:aff id="aff2"><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></nlm:aff></affiliation></author><author><name sortKey="Graziano, Robert F" sort="Graziano, Robert F" uniqKey="Graziano R" first="Robert F." last="Graziano">Robert F. Graziano</name><affiliation wicri:level="2"><nlm:aff id="aff4"><institution>Medarex, Inc.</institution>,<addr-line>Bloomsbury, New Jersey</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Bloomsbury</wicri:cityArea></affiliation></author><author><name sortKey="Srinivasan, Mohan" sort="Srinivasan, Mohan" uniqKey="Srinivasan M" first="Mohan" last="Srinivasan">Mohan Srinivasan</name><affiliation wicri:level="2"><nlm:aff id="aff4"><institution>Medarex, Inc.</institution>,<addr-line>Bloomsbury, New Jersey</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Bloomsbury</wicri:cityArea></affiliation></author><author><name sortKey="Lowy, Israel" sort="Lowy, Israel" uniqKey="Lowy I" first="Israel" last="Lowy">Israel Lowy</name><affiliation wicri:level="2"><nlm:aff id="aff4"><institution>Medarex, Inc.</institution>,<addr-line>Bloomsbury, New Jersey</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Bloomsbury</wicri:cityArea></affiliation></author><author><name sortKey="Finberg, Robert W" sort="Finberg, Robert W" uniqKey="Finberg R" first="Robert W" last="Finberg">Robert W. Finberg</name><affiliation><nlm:aff id="aff1"><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></nlm:aff></affiliation></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><affiliation wicri:level="2"><nlm:aff id="aff3"><institution>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Bethesda, Maryland</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name><affiliation wicri:level="2"><nlm:aff id="aff3"><institution>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Bethesda, Maryland</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Somasundaran, Mohan" sort="Somasundaran, Mohan" uniqKey="Somasundaran M" first="Mohan" last="Somasundaran">Mohan Somasundaran</name><affiliation><nlm:aff id="aff1"><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></nlm:aff></affiliation></author><author><name sortKey="Luzuriaga, Katherine" sort="Luzuriaga, Katherine" uniqKey="Luzuriaga K" first="Katherine" last="Luzuriaga">Katherine Luzuriaga</name><affiliation><nlm:aff id="aff1"><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></nlm:aff></affiliation></author><author><name sortKey="Sullivan, John L" sort="Sullivan, John L" uniqKey="Sullivan J" first="John L." last="Sullivan">John L. Sullivan</name><affiliation><nlm:aff id="aff1"><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ambrosino, Donna M" sort="Ambrosino, Donna M" uniqKey="Ambrosino D" first="Donna M." last="Ambrosino">Donna M. Ambrosino</name><affiliation><nlm:aff id="aff2"><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><p><bold><italic>Background.</italic></bold> Severe acute respiratory syndrome (SARS) remains a significant public health concern after the epidemic in 2003. Human monoclonal antibodies (MAbs) that neutralize SARS-associated coronavirus (SARSCoV) could provide protection for exposed individuals.</p><p><bold><italic>Methods.</italic></bold> Transgenic mice with human immunoglobulin genes were immunized with the recombinant major surface (S) glycoprotein ectodomain of SARS-CoV. Epitopes of 2 neutralizing MAbs derived from these mice were mapped and evaluated in a murine model of SARS-CoV infection.</p><p><bold><italic>Results.</italic></bold> Both MAbs bound to S glycoprotein expressed on transfected cells but differed in their ability to block binding of S glycoprotein to Vero E6 cells. Immunoprecipitation analysis revealed 2 antibody-binding epitopes: one MAb (201) bound within the receptor-binding domain at aa 490–510, and the other MAb (68) bound externally to the domain at aa 130–150. Mice that received 40 mg/kg of either MAb prior to challenge with SARS-CoV were completely protected from virus replication in the lungs, and doses as low as 1.6 mg/kg offered significant protection.</p><p><bold><italic>Conclusions.</italic></bold> Two neutralizing epitopes were defined for MAbs to SARS-CoV S glycoprotein. Antibodies to both epitopes protected mice against SARS-CoV challenge. Clinical trials are planned to test MAb 201, a fully human MAb specific for the epitope within the receptor-binding region.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Gunther, S" uniqKey="Gunther S">S Gunther</name></author><author><name sortKey="Preiser, W" uniqKey="Preiser W">W Preiser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ksiazek, Tg" uniqKey="Ksiazek T">TG Ksiazek</name></author><author><name sortKey="Erdman, D" uniqKey="Erdman D">D Erdman</name></author><author><name sortKey="Goldsmith, Cs" uniqKey="Goldsmith C">CS Goldsmith</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Bisht, H" uniqKey="Bisht H">H Bisht</name></author><author><name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name></author><author><name sortKey="Vogel, L" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">J. Infect. Dis</journal-id><journal-id journal-id-type="hwp">jinfdis</journal-id><journal-id journal-id-type="publisher-id">jid</journal-id><journal-title-group><journal-title>The Journal of Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">0022-1899</issn><issn pub-type="epub">1537-6613</issn><publisher><publisher-name>The University of Chicago Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">15655773</article-id><article-id pub-id-type="pmc">7110081</article-id><article-id pub-id-type="doi">10.1086/427242</article-id><article-categories><subj-group subj-group-type="heading"><subject>Major Articles and Brief Reports</subject><subj-group subj-group-type="category-toc-heading"><subject>Viruses</subject><subj-group subj-group-type="category-toc-heading"><subject>Major Articles</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Development and Characterization of a Severe Acute Respiratory Syndrome—Associated Coronavirus—Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Greenough</surname><given-names>Thomas C.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Babcock</surname><given-names>Gregory J.</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Roberts</surname><given-names>Anjeanette</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Hernandez</surname><given-names>Hector J.</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Thomas</surname><given-names>William D.</given-names><suffix>Jr.</suffix></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Coccia</surname><given-names>Jennifer A.</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Graziano</surname><given-names>Robert F.</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Srinivasan</surname><given-names>Mohan</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Lowy</surname><given-names>Israel</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Finberg</surname><given-names>Robert W</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Subbarao</surname><given-names>Kanta</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Vogel</surname><given-names>Leatrice</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Somasundaran</surname><given-names>Mohan</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Luzuriaga</surname><given-names>Katherine</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sullivan</surname><given-names>John L.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ambrosino</surname><given-names>Donna M.</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="corresp" rid="cor1"></xref><pmc-comment>donna.ambrosino@umassmed.edu </pmc-comment>
</contrib></contrib-group><aff id="aff1"><label>1</label><institution>Departments of Pediatrics and Medicine, Program in Molecular Medicine, University of Massachusetts Medical School</institution>,<addr-line>Worcester</addr-line></aff><aff id="aff2"><label>2</label><institution>Massachusetts Biologic Laboratories, University of Massachusetts Medical School</institution>,<addr-line>Jamaica Plain</addr-line></aff><aff id="aff3"><label>3</label><institution>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Bethesda, Maryland</addr-line></aff><aff id="aff4"><label>4</label><institution>Medarex, Inc.</institution>,<addr-line>Bloomsbury, New Jersey</addr-line></aff><author-notes><corresp id="cor1">Reprints or correspondence: Dr. Donna M. Ambrosino, <institution>Massachusetts Biologic Laboratories</institution>, <addr-line>305 South St., Jamaica Plain, MA 02130</addr-line> (<email>donna.ambrosino@umassmed.edu</email>).</corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>2</month><year>2005</year></pub-date><pub-date pub-type="epub" iso-8601-date="2005-02-15"><day>15</day><month>2</month><year>2005</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>2</month><year>2005</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>191</volume><issue>4</issue><fpage>507</fpage><lpage>514</lpage><history><date date-type="received"><day>24</day><month>6</month><year>2004</year></date><date date-type="accepted"><day>23</day><month>8</month><year>2004</year></date></history><permissions><copyright-statement>© 2005 by the Infectious Diseases Society of America</copyright-statement><copyright-year>2005</copyright-year><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.</license-p></license></permissions><self-uri xlink:href="191-4-507.pdf"></self-uri><abstract><title>Abstract</title><p><bold><italic>Background.</italic></bold> Severe acute respiratory syndrome (SARS) remains a significant public health concern after the epidemic in 2003. Human monoclonal antibodies (MAbs) that neutralize SARS-associated coronavirus (SARSCoV) could provide protection for exposed individuals.</p><p><bold><italic>Methods.</italic></bold> Transgenic mice with human immunoglobulin genes were immunized with the recombinant major surface (S) glycoprotein ectodomain of SARS-CoV. Epitopes of 2 neutralizing MAbs derived from these mice were mapped and evaluated in a murine model of SARS-CoV infection.</p><p><bold><italic>Results.</italic></bold> Both MAbs bound to S glycoprotein expressed on transfected cells but differed in their ability to block binding of S glycoprotein to Vero E6 cells. Immunoprecipitation analysis revealed 2 antibody-binding epitopes: one MAb (201) bound within the receptor-binding domain at aa 490–510, and the other MAb (68) bound externally to the domain at aa 130–150. Mice that received 40 mg/kg of either MAb prior to challenge with SARS-CoV were completely protected from virus replication in the lungs, and doses as low as 1.6 mg/kg offered significant protection.</p><p><bold><italic>Conclusions.</italic></bold> Two neutralizing epitopes were defined for MAbs to SARS-CoV S glycoprotein. Antibodies to both epitopes protected mice against SARS-CoV challenge. Clinical trials are planned to test MAb 201, a fully human MAb specific for the epitope within the receptor-binding region.</p></abstract></article-meta></front></pmc><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li><li>New Jersey</li></region></list><tree><noCountry><name sortKey="Ambrosino, Donna M" sort="Ambrosino, Donna M" uniqKey="Ambrosino D" first="Donna M." last="Ambrosino">Donna M. Ambrosino</name><name sortKey="Babcock, Gregory J" sort="Babcock, Gregory J" uniqKey="Babcock G" first="Gregory J." last="Babcock">Gregory J. Babcock</name><name sortKey="Coccia, Jennifer A" sort="Coccia, Jennifer A" uniqKey="Coccia J" first="Jennifer A." last="Coccia">Jennifer A. Coccia</name><name sortKey="Finberg, Robert W" sort="Finberg, Robert W" uniqKey="Finberg R" first="Robert W" last="Finberg">Robert W. Finberg</name><name sortKey="Greenough, Thomas C" sort="Greenough, Thomas C" uniqKey="Greenough T" first="Thomas C." last="Greenough">Thomas C. Greenough</name><name sortKey="Hernandez, Hector J" sort="Hernandez, Hector J" uniqKey="Hernandez H" first="Hector J." last="Hernandez">Hector J. Hernandez</name><name sortKey="Luzuriaga, Katherine" sort="Luzuriaga, Katherine" uniqKey="Luzuriaga K" first="Katherine" last="Luzuriaga">Katherine Luzuriaga</name><name sortKey="Somasundaran, Mohan" sort="Somasundaran, Mohan" uniqKey="Somasundaran M" first="Mohan" last="Somasundaran">Mohan Somasundaran</name><name sortKey="Sullivan, John L" sort="Sullivan, John L" uniqKey="Sullivan J" first="John L." last="Sullivan">John L. Sullivan</name><name sortKey="Thomas, William D" sort="Thomas, William D" uniqKey="Thomas W" first="William D." last="Thomas">William D. Thomas</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Roberts, Anjeanette" sort="Roberts, Anjeanette" uniqKey="Roberts A" first="Anjeanette" last="Roberts">Anjeanette Roberts</name></region><name sortKey="Graziano, Robert F" sort="Graziano, Robert F" uniqKey="Graziano R" first="Robert F." last="Graziano">Robert F. Graziano</name><name sortKey="Lowy, Israel" sort="Lowy, Israel" uniqKey="Lowy I" first="Israel" last="Lowy">Israel Lowy</name><name sortKey="Srinivasan, Mohan" sort="Srinivasan, Mohan" uniqKey="Srinivasan M" first="Mohan" last="Srinivasan">Mohan Srinivasan</name><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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