Serveur d'exploration MERS

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Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein

Identifieur interne : 001203 ( Pmc/Curation ); précédent : 001202; suivant : 001204

Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein

Auteurs : Junghyun Goo [Corée du Sud] ; Yuji Jeong [Corée du Sud] ; Young-Shin Park [Corée du Sud] ; Eunji Yang [Corée du Sud] ; Dae-Im Jung [Corée du Sud] ; Semi Rho [Corée du Sud] ; Uni Park [Corée du Sud] ; Hyeyeong Sung [Corée du Sud] ; Pil-Gu Park [Corée du Sud] ; Jung-Ah Choi [Corée du Sud] ; Sang Hwan Seo [Corée du Sud] ; Nam Hyuck Cho [Corée du Sud] ; Hyeja Lee [Corée du Sud] ; Jae Myun Lee [Corée du Sud] ; Jae-Ouk Kim [Corée du Sud] ; Manki Song [Corée du Sud]

Source :

RBID : PMC:7114870

Abstract

Highlights

Identification of neutralizing mAbs using MERS-CoV spike-pseudotyped virus.

Transmembrane domain-deleted spike subunit protein induced neutralizing antibodies.

Neutralizing antibodies could bind to RBD of MERS-CoV spike, but not vice versa.

Mutation in residue 506–509 or 529 of S elicits neutralization escape of MERS-CoV.

Our mAbs can be utilized for identification of specific mutation of MERS-CoV.


Url:
DOI: 10.1016/j.virusres.2020.197863
PubMed: 31945421
PubMed Central: 7114870

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Links to Exploration step

PMC:7114870

Le document en format XML

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<name sortKey="Seo, Sang Hwan" sort="Seo, Sang Hwan" uniqKey="Seo S" first="Sang Hwan" last="Seo">Sang Hwan Seo</name>
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<name sortKey="Cho, Nam Hyuck" sort="Cho, Nam Hyuck" uniqKey="Cho N" first="Nam Hyuck" last="Cho">Nam Hyuck Cho</name>
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<name sortKey="Kim, Jae Ouk" sort="Kim, Jae Ouk" uniqKey="Kim J" first="Jae-Ouk" last="Kim">Jae-Ouk Kim</name>
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<p id="par0005">Identification of neutralizing mAbs using MERS-CoV spike-pseudotyped virus.</p>
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<list-item id="lsti0010">
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<p id="par0010">Transmembrane domain-deleted spike subunit protein induced neutralizing antibodies.</p>
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<p id="par0015">Neutralizing antibodies could bind to RBD of MERS-CoV spike, but not vice versa.</p>
</list-item>
<list-item id="lsti0020">
<label></label>
<p id="par0020">Mutation in residue 506–509 or 529 of S elicits neutralization escape of MERS-CoV.</p>
</list-item>
<list-item id="lsti0025">
<label></label>
<p id="par0025">Our mAbs can be utilized for identification of specific mutation of MERS-CoV.</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">Virus Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Virus Res</journal-id>
<journal-title-group>
<journal-title>Virus Research</journal-title>
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<issn pub-type="ppub">0168-1702</issn>
<issn pub-type="epub">1872-7492</issn>
<publisher>
<publisher-name>The Authors. Published by Elsevier B.V.</publisher-name>
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</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">31945421</article-id>
<article-id pub-id-type="pmc">7114870</article-id>
<article-id pub-id-type="publisher-id">S0168-1702(19)30750-6</article-id>
<article-id pub-id-type="doi">10.1016/j.virusres.2020.197863</article-id>
<article-id pub-id-type="publisher-id">197863</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein</article-title>
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<contrib-group>
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<surname>Goo</surname>
<given-names>Junghyun</given-names>
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<xref rid="fn0005" ref-type="fn">1</xref>
</contrib>
<contrib contrib-type="author" id="aut0015">
<name>
<surname>Park</surname>
<given-names>Young-Shin</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
<xref rid="fn0005" ref-type="fn">1</xref>
</contrib>
<contrib contrib-type="author" id="aut0020">
<name>
<surname>Yang</surname>
<given-names>Eunji</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="aut0025">
<name>
<surname>Jung</surname>
<given-names>Dae-Im</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="aut0030">
<name>
<surname>Rho</surname>
<given-names>Semi</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="aut0035">
<name>
<surname>Park</surname>
<given-names>Uni</given-names>
</name>
<xref rid="aff0010" ref-type="aff">b</xref>
<xref rid="aff0015" ref-type="aff">c</xref>
</contrib>
<contrib contrib-type="author" id="aut0040">
<name>
<surname>Sung</surname>
<given-names>Hyeyeong</given-names>
</name>
<xref rid="aff0025" ref-type="aff">e</xref>
</contrib>
<contrib contrib-type="author" id="aut0045">
<name>
<surname>Park</surname>
<given-names>Pil-Gu</given-names>
</name>
<xref rid="aff0030" ref-type="aff">f</xref>
</contrib>
<contrib contrib-type="author" id="aut0050">
<name>
<surname>Choi</surname>
<given-names>Jung-ah</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="aut0055">
<name>
<surname>Seo</surname>
<given-names>Sang Hwan</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="aut0060">
<name>
<surname>Cho</surname>
<given-names>Nam Hyuck</given-names>
</name>
<xref rid="aff0010" ref-type="aff">b</xref>
<xref rid="aff0015" ref-type="aff">c</xref>
<xref rid="aff0020" ref-type="aff">d</xref>
</contrib>
<contrib contrib-type="author" id="aut0065">
<name>
<surname>Lee</surname>
<given-names>Hyeja</given-names>
</name>
<xref rid="aff0025" ref-type="aff">e</xref>
</contrib>
<contrib contrib-type="author" id="aut0070">
<name>
<surname>Lee</surname>
<given-names>Jae Myun</given-names>
</name>
<xref rid="aff0030" ref-type="aff">f</xref>
</contrib>
<contrib contrib-type="author" id="aut0075">
<name>
<surname>Kim</surname>
<given-names>Jae-Ouk</given-names>
</name>
<email>jokim@ivi.int</email>
<xref rid="aff0005" ref-type="aff">a</xref>
<xref rid="cor0005" ref-type="corresp">*</xref>
</contrib>
<contrib contrib-type="author" id="aut0080">
<name>
<surname>Song</surname>
<given-names>Manki</given-names>
</name>
<email>mksong@ivi.int</email>
<xref rid="aff0005" ref-type="aff">a</xref>
<xref rid="cor0005" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="aff0005">
<label>a</label>
Science Unit, International Vaccine Institute, Seoul, South Korea</aff>
<aff id="aff0010">
<label>b</label>
Department of Microbiology and Immunology, South Korea</aff>
<aff id="aff0015">
<label>c</label>
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea</aff>
<aff id="aff0020">
<label>d</label>
Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, South Korea</aff>
<aff id="aff0025">
<label>e</label>
NKMAX Co., Ltd., Seongnam, South Korea</aff>
<aff id="aff0030">
<label>f</label>
Department of Microbiology and Immunology, Brain Korea 21 PLUS Project for Medical Science, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea</aff>
<author-notes>
<corresp id="cor0005">
<label></label>
Corresponding authors.
<email>jokim@ivi.int</email>
<email>mksong@ivi.int</email>
</corresp>
<fn id="fn0005">
<label>1</label>
<p id="npar0005">These authors have equally contributed to this paper.</p>
</fn>
</author-notes>
<pub-date pub-type="pmc-release">
<day>13</day>
<month>1</month>
<year>2020</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">
<month>3</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>13</day>
<month>1</month>
<year>2020</year>
</pub-date>
<volume>278</volume>
<fpage>197863</fpage>
<lpage>197863</lpage>
<history>
<date date-type="received">
<day>18</day>
<month>10</month>
<year>2019</year>
</date>
<date date-type="rev-recd">
<day>2</day>
<month>1</month>
<year>2020</year>
</date>
<date date-type="accepted">
<day>10</day>
<month>1</month>
<year>2020</year>
</date>
</history>
<permissions>
<copyright-statement>© 2020 The Authors</copyright-statement>
<copyright-year>2020</copyright-year>
<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 abstract-type="author-highlights" id="abs0005">
<title>Highlights</title>
<p>
<list list-type="simple" id="lis0005">
<list-item id="lsti0005">
<label></label>
<p id="par0005">Identification of neutralizing mAbs using MERS-CoV spike-pseudotyped virus.</p>
</list-item>
<list-item id="lsti0010">
<label></label>
<p id="par0010">Transmembrane domain-deleted spike subunit protein induced neutralizing antibodies.</p>
</list-item>
<list-item id="lsti0015">
<label></label>
<p id="par0015">Neutralizing antibodies could bind to RBD of MERS-CoV spike, but not vice versa.</p>
</list-item>
<list-item id="lsti0020">
<label></label>
<p id="par0020">Mutation in residue 506–509 or 529 of S elicits neutralization escape of MERS-CoV.</p>
</list-item>
<list-item id="lsti0025">
<label></label>
<p id="par0025">Our mAbs can be utilized for identification of specific mutation of MERS-CoV.</p>
</list-item>
</list>
</p>
</abstract>
<abstract id="abs0010">
<p>Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe pulmonary infection, with ∼35 % mortality. Spike glycoprotein (S) of MERS-CoV is a key target for vaccines and therapeutics because S mediates viral entry and membrane-fusion to host cells. Here, four different S subunit proteins, receptor-binding domain (RBD; 358–606 aa), S1 (1–751 aa), S2 (752–1296 aa), and SΔTM (1–1296 aa), were generated using the baculoviral system and immunized in mice to develop neutralizing antibodies. We developed 77 hybridomas and selected five neutralizing mAbs by immunization with SΔTM against MERS-CoV EMC/2012 strain S-pseudotyped lentivirus. However, all five monoclonal antibodies (mAb) did not neutralize the pseudotyped V534A mutation. Additionally, one mAb RBD-14F8 did not show neutralizing activity against pseudoviruses with amino acid substitution of L506 F or D509 G (England1 strain, EMC/2012 L506 F, and EMC/2012 D509 G), and RBD-43E4 mAb could not neutralize the pseudotyped I529 T mutation, while three other neutralizing mAbs showed broad neutralizing activity. This implies that the mutation in residue 506–509, 529, and 534 of S is critical to generate neutralization escape variants of MERS-CoV. Interestingly, all five neutralizing mAbs have binding affinity to RBD, although most mAbs generated by RBD did not have neutralizing activity. Additionally, chimeric antibodies of RBD-14F8 and RBD-43E4 with human Fc and light chain showed neutralizing effect against wild type MERS-CoV KOR/KNIH/002, similar to the original mouse mAbs. Thus, our mAbs can be utilized for the identification of specific mutations of MERS-CoV.</p>
</abstract>
<kwd-group id="kwd0005">
<title>Keywords</title>
<kwd>MERS-CoV</kwd>
<kwd>Monoclonal antibody</kwd>
<kwd>Neutralizing antibody</kwd>
<kwd>Pseudovirus</kwd>
<kwd>Neutralization</kwd>
<kwd>Epitope</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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