Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology
Identifieur interne : 000816 ( Pmc/Corpus ); précédent : 000815; suivant : 000817Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology
Auteurs : Jody D. Berry ; Kevin Hay ; James M. Rini ; Meng Yu ; Linfa Wang ; Francis A. Plummer ; Cindi R. Corbett ; Anton AndonovSource :
- mAbs [ 1942-0862 ] ; 2010.
Abstract
Neutralizing antibody responses to the surface glycoproteins of enveloped viruses play an important role in immunity. Many of these glycoproteins, including the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) protein form trimeric units in the membrane of the native virion. There is substantial experimental and pre-clinical evidence showing that the S protein is a promising lead for vaccines and therapeutics. Previously we generated a panel of monoclonal antibodies (mAbs) to whole inactivated SARS-CoV which neutralize the virus in vitro.
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PubMed: 20168090
PubMed Central: 2828578
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PMC:2828578Le document en format XML
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<author><name sortKey="Berry, Jody D" sort="Berry, Jody D" uniqKey="Berry J" first="Jody D" last="Berry">Jody D. Berry</name>
<affiliation><nlm:aff id="A1">Department of Medical Microbiology; University of Manitoba; Winnipeg, CA</nlm:aff>
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<affiliation><nlm:aff id="A2">National Microbiology Laboratory; Health Canada; Winnipeg, Canada</nlm:aff>
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<affiliation><nlm:aff id="A3">Department of Immunology; University of Manitoba; Winnipeg, CA</nlm:aff>
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<author><name sortKey="Hay, Kevin" sort="Hay, Kevin" uniqKey="Hay K" first="Kevin" last="Hay">Kevin Hay</name>
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<author><name sortKey="Rini, James M" sort="Rini, James M" uniqKey="Rini J" first="James M" last="Rini">James M. Rini</name>
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<author><name sortKey="Yu, Meng" sort="Yu, Meng" uniqKey="Yu M" first="Meng" last="Yu">Meng Yu</name>
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<author><name sortKey="Wang, Linfa" sort="Wang, Linfa" uniqKey="Wang L" first="Linfa" last="Wang">Linfa Wang</name>
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<author><name sortKey="Corbett, Cindi R" sort="Corbett, Cindi R" uniqKey="Corbett C" first="Cindi R" last="Corbett">Cindi R. Corbett</name>
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<author><name sortKey="Andonov, Anton" sort="Andonov, Anton" uniqKey="Andonov A" first="Anton" last="Andonov">Anton Andonov</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology</title>
<author><name sortKey="Berry, Jody D" sort="Berry, Jody D" uniqKey="Berry J" first="Jody D" last="Berry">Jody D. Berry</name>
<affiliation><nlm:aff id="A1">Department of Medical Microbiology; University of Manitoba; Winnipeg, CA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">National Microbiology Laboratory; Health Canada; Winnipeg, Canada</nlm:aff>
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<affiliation><nlm:aff id="A3">Department of Immunology; University of Manitoba; Winnipeg, CA</nlm:aff>
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<author><name sortKey="Hay, Kevin" sort="Hay, Kevin" uniqKey="Hay K" first="Kevin" last="Hay">Kevin Hay</name>
<affiliation><nlm:aff id="A3">Department of Immunology; University of Manitoba; Winnipeg, CA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rini, James M" sort="Rini, James M" uniqKey="Rini J" first="James M" last="Rini">James M. Rini</name>
<affiliation><nlm:aff id="A4">Departments of Molecular Genetics and Biochemistry; University of Toronto; Toronto, CA</nlm:aff>
</affiliation>
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<author><name sortKey="Yu, Meng" sort="Yu, Meng" uniqKey="Yu M" first="Meng" last="Yu">Meng Yu</name>
<affiliation><nlm:aff id="A5">CSIRO Livestock Industries; Australian Animal Health Laboratory; Geelong, Victoria Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Linfa" sort="Wang, Linfa" uniqKey="Wang L" first="Linfa" last="Wang">Linfa Wang</name>
<affiliation><nlm:aff id="A5">CSIRO Livestock Industries; Australian Animal Health Laboratory; Geelong, Victoria Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Plummer, Francis A" sort="Plummer, Francis A" uniqKey="Plummer F" first="Francis A" last="Plummer">Francis A. Plummer</name>
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</affiliation>
<affiliation><nlm:aff id="A2">National Microbiology Laboratory; Health Canada; Winnipeg, Canada</nlm:aff>
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<author><name sortKey="Corbett, Cindi R" sort="Corbett, Cindi R" uniqKey="Corbett C" first="Cindi R" last="Corbett">Cindi R. Corbett</name>
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<affiliation><nlm:aff id="A2">National Microbiology Laboratory; Health Canada; Winnipeg, Canada</nlm:aff>
</affiliation>
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<author><name sortKey="Andonov, Anton" sort="Andonov, Anton" uniqKey="Andonov A" first="Anton" last="Andonov">Anton Andonov</name>
<affiliation><nlm:aff id="A1">Department of Medical Microbiology; University of Manitoba; Winnipeg, CA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">National Microbiology Laboratory; Health Canada; Winnipeg, Canada</nlm:aff>
</affiliation>
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<series><title level="j">mAbs</title>
<idno type="ISSN">1942-0862</idno>
<idno type="eISSN">1942-0870</idno>
<imprint><date when="2010">2010</date>
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<front><div type="abstract" xml:lang="en"><p>Neutralizing antibody responses to the surface glycoproteins of enveloped viruses play an important role in immunity. Many of these glycoproteins, including the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) protein form trimeric units in the membrane of the native virion. There is substantial experimental and pre-clinical evidence showing that the S protein is a promising lead for vaccines and therapeutics. Previously we generated a panel of monoclonal antibodies (mAbs) to whole inactivated SARS-CoV which neutralize the virus in vitro.<xref ref-type="bibr" rid="R1">1</xref>
,<xref ref-type="bibr" rid="R2">2</xref>
Here, we define their specificity and affinity, map several of their epitopes and lastly characterise chimeric versions of them. Our data show that the neutralizing mAbs bind to the angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD) of the SARS S protein. Three of the chimeric mAbs retain their binding specificity while one conformational mAb, F26G19, lost its ability to bind the S protein despite high level expression. The affinity for recombinant S is maintained in all of the functional chimeric versions of the parental mAbs. Both parental mAb F26G18 and the chimeric version neutralize the TOR2 strain of SARS-CoV with essentially identical titres (2.07 and 2.47 nM, respectively). Lastly, a comparison with other neutralizing mAbs to SARS-CoV clearly shows that the dominance of a 33 amino acid residue loop of the SARS-CoV RBD is independent of repertoire, species, quaternary structure, and importantly, the technology used to derive the mAbs. In cases like this, the dominance of a compact RBD antigenic domain and the central role of the S protein in pathogenesis may inherently create immunoselection pressure on viruses to evolve more complex evasion strategies or die out of a host species. The apparent simplicity of the mechanism of SARS-CoV neutralization is in stark contrast to the complexity shown by other enveloped viruses.</p>
</div>
</front>
</TEI>
<pmc article-type="brief-report"><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">MAbs</journal-id>
<journal-id journal-id-type="publisher-id">mAbs</journal-id>
<journal-title-group><journal-title>mAbs</journal-title>
</journal-title-group>
<issn pub-type="ppub">1942-0862</issn>
<issn pub-type="epub">1942-0870</issn>
<publisher><publisher-name>Landes Bioscience</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">20168090</article-id>
<article-id pub-id-type="pmc">2828578</article-id>
<article-id pub-id-type="publisher-id">1942-0862-2-1-7</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Report</subject>
</subj-group>
</article-categories>
<title-group><article-title>Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Berry</surname>
<given-names>Jody D</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hay</surname>
<given-names>Kevin</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rini</surname>
<given-names>James M</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yu</surname>
<given-names>Meng</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Linfa</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Plummer</surname>
<given-names>Francis A</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Corbett</surname>
<given-names>Cindi R</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Andonov</surname>
<given-names>Anton</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<aff id="A1"><label>1</label>
Department of Medical Microbiology; University of Manitoba; Winnipeg, CA</aff>
<aff id="A2"><label>2</label>
National Microbiology Laboratory; Health Canada; Winnipeg, Canada</aff>
<aff id="A3"><label>3</label>
Department of Immunology; University of Manitoba; Winnipeg, CA</aff>
<aff id="A4"><label>4</label>
Departments of Molecular Genetics and Biochemistry; University of Toronto; Toronto, CA</aff>
<aff id="A5"><label>5</label>
CSIRO Livestock Industries; Australian Animal Health Laboratory; Geelong, Victoria Australia</aff>
</contrib-group>
<author-notes><corresp>Correspondence to: Jody D. Berry; Email: <email>jberry@cangene.com</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><season>Jan-Feb</season>
<year>2010</year>
</pub-date>
<volume>2</volume>
<issue>1</issue>
<fpage>53</fpage>
<lpage>66</lpage>
<history><date date-type="received"><day>29</day>
<month>10</month>
<year>2009</year>
</date>
<date date-type="accepted"><day>27</day>
<month>11</month>
<year>2009</year>
</date>
</history>
<permissions><copyright-statement>© 2010 Landes Bioscience</copyright-statement>
<copyright-year>2010</copyright-year>
</permissions>
<abstract><p>Neutralizing antibody responses to the surface glycoproteins of enveloped viruses play an important role in immunity. Many of these glycoproteins, including the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) protein form trimeric units in the membrane of the native virion. There is substantial experimental and pre-clinical evidence showing that the S protein is a promising lead for vaccines and therapeutics. Previously we generated a panel of monoclonal antibodies (mAbs) to whole inactivated SARS-CoV which neutralize the virus in vitro.<xref ref-type="bibr" rid="R1">1</xref>
,<xref ref-type="bibr" rid="R2">2</xref>
Here, we define their specificity and affinity, map several of their epitopes and lastly characterise chimeric versions of them. Our data show that the neutralizing mAbs bind to the angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD) of the SARS S protein. Three of the chimeric mAbs retain their binding specificity while one conformational mAb, F26G19, lost its ability to bind the S protein despite high level expression. The affinity for recombinant S is maintained in all of the functional chimeric versions of the parental mAbs. Both parental mAb F26G18 and the chimeric version neutralize the TOR2 strain of SARS-CoV with essentially identical titres (2.07 and 2.47 nM, respectively). Lastly, a comparison with other neutralizing mAbs to SARS-CoV clearly shows that the dominance of a 33 amino acid residue loop of the SARS-CoV RBD is independent of repertoire, species, quaternary structure, and importantly, the technology used to derive the mAbs. In cases like this, the dominance of a compact RBD antigenic domain and the central role of the S protein in pathogenesis may inherently create immunoselection pressure on viruses to evolve more complex evasion strategies or die out of a host species. The apparent simplicity of the mechanism of SARS-CoV neutralization is in stark contrast to the complexity shown by other enveloped viruses.</p>
</abstract>
<kwd-group><title>Key words</title>
<kwd>SARS coronavirus</kwd>
<kwd>monoclonal antibody</kwd>
<kwd>neutralizing</kwd>
<kwd>epitope</kwd>
<kwd>immunochemistry</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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