Serveur d'exploration MERS

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Ultrapotent Human Neutralizing Antibody Repertoires Against Middle East Respiratory Syndrome Coronavirus From a Recovered Patient

Identifieur interne : 000444 ( Pmc/Checkpoint ); précédent : 000443; suivant : 000445

Ultrapotent Human Neutralizing Antibody Repertoires Against Middle East Respiratory Syndrome Coronavirus From a Recovered Patient

Auteurs : Peihua Niu [République populaire de Chine] ; Senyan Zhang [République populaire de Chine] ; Panpan Zhou [République populaire de Chine] ; Baoying Huang [République populaire de Chine] ; Yao Deng [République populaire de Chine] ; Kun Qin [République populaire de Chine] ; Pengfei Wang [République populaire de Chine] ; Wenling Wang [République populaire de Chine] ; Xinquan Wang [République populaire de Chine] ; Jianfang Zhou [République populaire de Chine] ; Linqi Zhang [République populaire de Chine] ; Wenjie Tan [République populaire de Chine]

Source :

RBID : PMC:7107445

Abstract

We describe the MERS-CoV-neutralizing antibody repertoires from a survivor and characterized 13 ultrapotent mAbs. The mAbs, MERS-GD27 and MERS-GD33, exhibited the strongest neutralizing activities. Both targeted receptor-binding domain via different contacts. The epitopes of MERS-GD27 overlapped with DPP4-binding sites.


Url:
DOI: 10.1093/infdis/jiy311
PubMed: 29846635
PubMed Central: 7107445


Affiliations:


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PMC:7107445

Le document en format XML

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<p>We describe the MERS-CoV-neutralizing antibody repertoires from a survivor and characterized 13 ultrapotent mAbs. The mAbs, MERS-GD27 and MERS-GD33, exhibited the strongest neutralizing activities. Both targeted receptor-binding domain via different contacts. The epitopes of MERS-GD27 overlapped with DPP4-binding sites.</p>
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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">J Infect Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Infect. Dis</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>Oxford University Press</publisher-name>
<publisher-loc>US</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">29846635</article-id>
<article-id pub-id-type="pmc">7107445</article-id>
<article-id pub-id-type="doi">10.1093/infdis/jiy311</article-id>
<article-id pub-id-type="publisher-id">jiy311</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>
</article-categories>
<title-group>
<article-title>Ultrapotent Human Neutralizing Antibody Repertoires Against Middle East Respiratory Syndrome Coronavirus From a Recovered Patient</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Niu</surname>
<given-names>Peihua</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="author-notes" rid="fn-0010"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhang</surname>
<given-names>Senyan</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
<xref ref-type="author-notes" rid="fn-0010"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhou</surname>
<given-names>Panpan</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
<xref ref-type="author-notes" rid="fn-0010"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huang</surname>
<given-names>Baoying</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="author-notes" rid="fn-0010"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Deng</surname>
<given-names>Yao</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Qin</surname>
<given-names>Kun</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Pengfei</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Wenling</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Xinquan</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhou</surname>
<given-names>Jianfang</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="author-notes" rid="fn-0020"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhang</surname>
<given-names>Linqi</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
<xref ref-type="author-notes" rid="fn-0020"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tan</surname>
<given-names>Wenjie</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="author-notes" rid="fn-0020"></xref>
<xref ref-type="corresp" rid="c1"></xref>
<pmc-comment>tanwj28@163.com</pmc-comment>
</contrib>
</contrib-group>
<aff id="AF0001">
<label>1</label>
MOH Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China</aff>
<aff id="AF0002">
<label>2</label>
The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, China</aff>
<author-notes>
<corresp id="c1">Correspondence: W. Tan, MD, PhD, Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155, Changbai Road, Changping district, Beijing, China (
<email>tanwj28@163.com</email>
).</corresp>
<fn id="fn-0010">
<p>P. N., S. Z., P. Z., and B. H. contributed equally to this work.</p>
</fn>
<fn id="fn-0020">
<p>J. Zhou, L. Zhang and W. Tan contributed equally.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<day>15</day>
<month>10</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="epub" iso-8601-date="2018-05-28">
<day>28</day>
<month>5</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>08</day>
<month>9</month>
<year>2019</year>
</pub-date>
<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the . </pmc-comment>
<volume>218</volume>
<issue>8</issue>
<fpage>1249</fpage>
<lpage>1260</lpage>
<history>
<date date-type="received">
<day>28</day>
<month>5</month>
<year>2018</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>5</month>
<year>2018</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</copyright-statement>
<copyright-year>2018</copyright-year>
<license license-type="oup-standard" xlink:href="https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model">
<license-p>This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (
<ext-link ext-link-type="uri" xlink:href="https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model">https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model</ext-link>
)</license-p>
</license>
<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="jiy311.pdf"></self-uri>
<abstract abstract-type="teaser">
<p>We describe the MERS-CoV-neutralizing antibody repertoires from a survivor and characterized 13 ultrapotent mAbs. The mAbs, MERS-GD27 and MERS-GD33, exhibited the strongest neutralizing activities. Both targeted receptor-binding domain via different contacts. The epitopes of MERS-GD27 overlapped with DPP4-binding sites.</p>
</abstract>
<abstract>
<title>Abstract</title>
<sec id="s1">
<title>Background</title>
<p>The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infection with a high (~35%) mortality rate. Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease.</p>
</sec>
<sec id="s2">
<title>Methods</title>
<p>We describe the germline diversity and neutralizing activity of 13 potent human monoclonal antibodies (mAbs) that target the MERS-CoV spike (S) protein. Biological functions were assessed by live MERS-CoV, pseudotype particle and its variants, and structural basis was also determined by crystallographic analysis.</p>
</sec>
<sec id="s3">
<title>Results</title>
<p>Of the 13 mAbs displaying strong neutralizing activity against MERS-CoV, two with the immunoglobulin heavy-chain variable region (IGHV)1-69-derived heavy chain (named MERS-GD27 and MERS-GD33) showed the most potent neutralizing activity against pseudotyped and live MERS-CoV in vitro. Mutagenesis analysis suggested that MERS-GD27 and MERS-GD33 recognized distinct regions in S glycoproteins, and the combination of 2 mAbs demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. The structural basis of MERS-GD27 neutralization and recognition revealed that its epitope almost completely overlapped with the receptor-binding site.</p>
</sec>
<sec id="s4">
<title>Conclusions</title>
<p>Our data provide new insights into the specific antibody repertoires and the molecular determinants of neutralization during natural MERS-CoV infection in humans. This finding supports additional efforts to design and develop novel therapies to combat MERS-CoV infections in humans.</p>
</sec>
</abstract>
<kwd-group>
<kwd>crystallographic analysis</kwd>
<kwd>human monoclonal antibody</kwd>
<kwd>MERS-CoV</kwd>
<kwd>neutralizing antibody repertoires</kwd>
</kwd-group>
<funding-group>
<award-group award-type="grant">
<funding-source>
<named-content content-type="funder-name">National Key Research and Development Program of China</named-content>
</funding-source>
<award-id>2016YFD0500300</award-id>
<award-id>2016YFC1200901</award-id>
<award-id>2016YFC1200200</award-id>
</award-group>
<award-group award-type="grant">
<funding-source>
<named-content content-type="funder-name">Megaproject for Infectious Disease Research of China</named-content>
</funding-source>
<award-id>2016ZX10004001-003</award-id>
</award-group>
</funding-group>
<counts>
<page-count count="12"></page-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
<settlement>
<li>Pékin</li>
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<name sortKey="Zhang, Senyan" sort="Zhang, Senyan" uniqKey="Zhang S" first="Senyan" last="Zhang">Senyan Zhang</name>
<name sortKey="Zhou, Jianfang" sort="Zhou, Jianfang" uniqKey="Zhou J" first="Jianfang" last="Zhou">Jianfang Zhou</name>
<name sortKey="Zhou, Panpan" sort="Zhou, Panpan" uniqKey="Zhou P" first="Panpan" last="Zhou">Panpan Zhou</name>
</country>
</tree>
</affiliations>
</record>

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