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Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse®

Identifieur interne : 001555 ( Pmc/Curation ); précédent : 001554; suivant : 001556

Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse®

Auteurs : Melissa Coughlin [États-Unis] ; Gin Lou [États-Unis] ; Osvaldo Martinez [États-Unis] ; Stephanie K. Masterman [Canada] ; Ole A. Olsen [Canada] ; Angelica A. Moksa [Canada] ; Michael Farzan [États-Unis] ; John S. Babcook [Canada] ; Bellur S. Prabhakar [États-Unis]

Source :

RBID : PMC:7103293

Abstract

Passive therapy with neutralizing human monoclonal antibodies (mAbs) could be an effective therapy against severe acute respiratory syndrome coronavirus (SARS-CoV). Utilizing the human immunoglobulin transgenic mouse, XenoMouse®, we produced fully human SARS-CoV spike (S) protein specific antibodies. Antibodies were examined for reactivity against a recombinant S1 protein, to which 200 antibodies reacted. Twenty-seven antibodies neutralized 200TCID50 SARS-CoV (Urbani). Additionally, 57 neutralizing antibodies were found that are likely specific to S2. Mapping of the binding region was achieved with several S1 recombinant proteins. Most S1 reactive neutralizing mAbs bound to the RBD, aa 318–510. However, two S1 specific mAbs reacted with a domain upstream of the RBD between aa 12 and 261. Immunoglobulin gene sequence analyses suggested at least 8 different binding specificities. Unique human mAbs could be used as a cocktail that would simultaneously target several neutralizing epitopes and prevent emergence of escape mutants.


Url:
DOI: 10.1016/j.virol.2006.09.029
PubMed: 17161858
PubMed Central: 7103293

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PMC:7103293

Le document en format XML

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<p>Passive therapy with neutralizing human monoclonal antibodies (mAbs) could be an effective therapy against severe acute respiratory syndrome coronavirus (SARS-CoV). Utilizing the human immunoglobulin transgenic mouse, XenoMouse®, we produced fully human SARS-CoV spike (S) protein specific antibodies. Antibodies were examined for reactivity against a recombinant S1 protein, to which 200 antibodies reacted. Twenty-seven antibodies neutralized 200TCID
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Virology</journal-id>
<journal-id journal-id-type="iso-abbrev">Virology</journal-id>
<journal-title-group>
<journal-title>Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0042-6822</issn>
<issn pub-type="epub">1096-0341</issn>
<publisher>
<publisher-name>Elsevier Inc.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">17161858</article-id>
<article-id pub-id-type="pmc">7103293</article-id>
<article-id pub-id-type="publisher-id">S0042-6822(06)00685-4</article-id>
<article-id pub-id-type="doi">10.1016/j.virol.2006.09.029</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse
<sup>®</sup>
</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Coughlin</surname>
<given-names>Melissa</given-names>
</name>
<xref rid="aff1" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lou</surname>
<given-names>Gin</given-names>
</name>
<xref rid="aff1" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Martinez</surname>
<given-names>Osvaldo</given-names>
</name>
<xref rid="aff1" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Masterman</surname>
<given-names>Stephanie K.</given-names>
</name>
<xref rid="aff2" ref-type="aff">c</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Olsen</surname>
<given-names>Ole A.</given-names>
</name>
<xref rid="aff2" ref-type="aff">c</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Moksa</surname>
<given-names>Angelica A.</given-names>
</name>
<xref rid="aff2" ref-type="aff">c</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Farzan</surname>
<given-names>Michael</given-names>
</name>
<xref rid="aff3" ref-type="aff">b</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Babcook</surname>
<given-names>John S.</given-names>
</name>
<xref rid="aff2" ref-type="aff">c</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Prabhakar</surname>
<given-names>Bellur S.</given-names>
</name>
<email>bprabhak@uic.edu</email>
<xref rid="aff1" ref-type="aff">a</xref>
<xref rid="cor1" ref-type="corresp"></xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>a</label>
Department of Microbiology and Immunology (MC790) College of Medicine, University of Illinois at Chicago, Room E705. 835 S. Wolcott AveChicago, IL 60612, USA</aff>
<aff id="aff3">
<label>b</label>
Partners AIDS Reasearch Center, Bringham and Women’s Hospital, Department of Medicine (Microbiology and Molecular Genetics), Harvard Medical School, 75 Francis Street Boston, MA 02115, USA</aff>
<aff id="aff2">
<label>c</label>
Amgen British Columbia Inc., 7990 Enterprise Street Burnaby, Canada BC V5A 1V7</aff>
<author-notes>
<corresp id="cor1">
<label></label>
Corresponding author. Fax: +1 312 996 6415.
<email>bprabhak@uic.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="pmc-release">
<day>11</day>
<month>12</month>
<year>2006</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub">
<day>25</day>
<month>4</month>
<year>2007</year>
</pub-date>
<pub-date pub-type="epub">
<day>11</day>
<month>12</month>
<year>2006</year>
</pub-date>
<volume>361</volume>
<issue>1</issue>
<fpage>93</fpage>
<lpage>102</lpage>
<history>
<date date-type="received">
<day>3</day>
<month>8</month>
<year>2006</year>
</date>
<date date-type="rev-recd">
<day>11</day>
<month>9</month>
<year>2006</year>
</date>
<date date-type="accepted">
<day>20</day>
<month>9</month>
<year>2006</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2006 Elsevier Inc. All rights reserved.</copyright-statement>
<copyright-year>2006</copyright-year>
<copyright-holder>Elsevier Inc.</copyright-holder>
<license>
<license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p>
</license>
</permissions>
<abstract>
<p>Passive therapy with neutralizing human monoclonal antibodies (mAbs) could be an effective therapy against severe acute respiratory syndrome coronavirus (SARS-CoV). Utilizing the human immunoglobulin transgenic mouse, XenoMouse®, we produced fully human SARS-CoV spike (S) protein specific antibodies. Antibodies were examined for reactivity against a recombinant S1 protein, to which 200 antibodies reacted. Twenty-seven antibodies neutralized 200TCID
<sub>50</sub>
SARS-CoV (Urbani). Additionally, 57 neutralizing antibodies were found that are likely specific to S2. Mapping of the binding region was achieved with several S1 recombinant proteins. Most S1 reactive neutralizing mAbs bound to the RBD, aa 318–510. However, two S1 specific mAbs reacted with a domain upstream of the RBD between aa 12 and 261. Immunoglobulin gene sequence analyses suggested at least 8 different binding specificities. Unique human mAbs could be used as a cocktail that would simultaneously target several neutralizing epitopes and prevent emergence of escape mutants.</p>
</abstract>
<kwd-group>
<title>Keywords</title>
<kwd>Severe acute respiratory syndrome coronavirus</kwd>
<kwd>SARS-CoV</kwd>
<kwd>Human monoclonal antibodies</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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