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Evaluation of Serologic and Antigenic Relationships Between Middle Eastern Respiratory Syndrome Coronavirus and Other Coronaviruses to Develop Vaccine Platforms for the Rapid Response to Emerging Coronaviruses

Identifieur interne : 000987 ( Pmc/Checkpoint ); précédent : 000986; suivant : 000988

Evaluation of Serologic and Antigenic Relationships Between Middle Eastern Respiratory Syndrome Coronavirus and Other Coronaviruses to Develop Vaccine Platforms for the Rapid Response to Emerging Coronaviruses

Auteurs : Sudhakar Agnihothram ; Robin Gopal [Royaume-Uni] ; Boyd L. Yount ; Eric F. Donaldson ; Vineet D. Menachery ; Rachel L. Graham ; Trevor D. Scobey ; Lisa E. Gralinski ; Mark R. Denison [États-Unis] ; Maria Zambon [Royaume-Uni] ; Ralph S. Baric

Source :

RBID : PMC:3952667

Abstract

Abstract

Background. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs.

Methods. Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs.

Results. Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43.

Conclusions. Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.


Url:
DOI: 10.1093/infdis/jit609
PubMed: 24253287
PubMed Central: 3952667


Affiliations:


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PMC:3952667

Le document en format XML

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<name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name>
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,
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<addr-line>Chapel Hill</addr-line>
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<affiliation>
<nlm:aff id="af2">
<addr-line>Department of Microbiology and Immunology</addr-line>
,
<institution>University of North Carolina</institution>
,
<addr-line>Chapel Hill</addr-line>
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,
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<addr-line>Chapel Hill</addr-line>
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<addr-line>Departments of Pediatrics and Microbiology and Immunology</addr-line>
,
<institution>Vanderbilt University</institution>
,
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<affiliation wicri:level="1">
<nlm:aff id="af4">
<addr-line>Viral Zoonosis Unit</addr-line>
,
<institution>Public Health of England</institution>
,
<addr-line>London</addr-line>
,
<country>United Kingdom</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name>
<affiliation>
<nlm:aff id="af1">
<addr-line>Department of Epidemiology</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="af2">
<addr-line>Department of Microbiology and Immunology</addr-line>
,
<institution>University of North Carolina</institution>
,
<addr-line>Chapel Hill</addr-line>
</nlm:aff>
</affiliation>
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<title level="j">The Journal of Infectious Diseases</title>
<idno type="ISSN">0022-1899</idno>
<idno type="eISSN">1537-6613</idno>
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<date when="2013">2013</date>
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<p>
<bold>
<italic>Background.</italic>
</bold>
 Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs.</p>
<p>
<bold>
<italic>Methods.</italic>
</bold>
 Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs.</p>
<p>
<bold>
<italic>Results.</italic>
</bold>
 Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43.</p>
<p>
<bold>
<italic>Conclusions.</italic>
</bold>
 Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.</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-id journal-id-type="hwp">jinfdis</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>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">24253287</article-id>
<article-id pub-id-type="pmc">3952667</article-id>
<article-id pub-id-type="doi">10.1093/infdis/jit609</article-id>
<article-id pub-id-type="publisher-id">jit609</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>Evaluation of Serologic and Antigenic Relationships Between Middle Eastern Respiratory Syndrome Coronavirus and Other Coronaviruses to Develop Vaccine Platforms for the Rapid Response to Emerging Coronaviruses</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Agnihothram</surname>
<given-names>Sudhakar</given-names>
</name>
<author-comment>
<title>a</title>
<p>S. A. and R. G. contributed equally to this work.</p>
</author-comment>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
<pmc-comment>rbaric@email.unc.edu</pmc-comment>
<xref ref-type="corresp" rid="d802670e282"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gopal</surname>
<given-names>Robin</given-names>
</name>
<author-comment>
<title>a</title>
<p>S. A. and R. G. contributed equally to this work.</p>
</author-comment>
<xref ref-type="aff" rid="af4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yount</surname>
<given-names>Boyd L.</given-names>
<suffix>Jr</suffix>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Donaldson</surname>
<given-names>Eric F.</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Menachery</surname>
<given-names>Vineet D.</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Graham</surname>
<given-names>Rachel L.</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Scobey</surname>
<given-names>Trevor D.</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gralinski</surname>
<given-names>Lisa E.</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Denison</surname>
<given-names>Mark R.</given-names>
</name>
<xref ref-type="aff" rid="af3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zambon</surname>
<given-names>Maria</given-names>
</name>
<xref ref-type="aff" rid="af4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Baric</surname>
<given-names>Ralph S.</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
</contrib>
</contrib-group>
<aff id="af1">
<label>1</label>
<addr-line>Department of Epidemiology</addr-line>
</aff>
<aff id="af2">
<label>2</label>
<addr-line>Department of Microbiology and Immunology</addr-line>
,
<institution>University of North Carolina</institution>
,
<addr-line>Chapel Hill</addr-line>
</aff>
<aff id="af3">
<label>3</label>
<addr-line>Departments of Pediatrics and Microbiology and Immunology</addr-line>
,
<institution>Vanderbilt University</institution>
,
<addr-line>Nashville, Tennessee</addr-line>
</aff>
<aff id="af4">
<label>4</label>
<addr-line>Viral Zoonosis Unit</addr-line>
,
<institution>Public Health of England</institution>
,
<addr-line>London</addr-line>
,
<country>United Kingdom</country>
</aff>
<author-notes>
<fn>
<p>Presented in part: MERS-CoV study group meeting June 20-22, 2013, Cairo, Egypt.</p>
</fn>
<fn id="AN1" fn-type="con">
<label>a</label>
<p>S. A. and R. G. contributed equally to this work.</p>
</fn>
<corresp id="d802670e282">Correspondence: Ralph S. Baric, PhD, Department of Microbiology and Immunology, 3304 Michael Hooker Research Bldg, Campus Box 7435, Chapel Hill, NC 27599-7435 (
<email>rbaric@email.unc.edu</email>
).</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>1</day>
<month>4</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub" iso-8601-date="2013-11-18">
<day>18</day>
<month>11</month>
<year>2013</year>
</pub-date>
<volume>209</volume>
<issue>7</issue>
<fpage>995</fpage>
<lpage>1006</lpage>
<history>
<date date-type="received">
<day>16</day>
<month>8</month>
<year>2013</year>
</date>
<date date-type="accepted">
<day>11</day>
<month>10</month>
<year>2013</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:
<email>journals.permissions@oup.com</email>
.</copyright-statement>
<copyright-year>2013</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="jit609.pdf"></self-uri>
<abstract>
<title>Abstract</title>
<p>
<bold>
<italic>Background.</italic>
</bold>
 Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs.</p>
<p>
<bold>
<italic>Methods.</italic>
</bold>
 Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs.</p>
<p>
<bold>
<italic>Results.</italic>
</bold>
 Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43.</p>
<p>
<bold>
<italic>Conclusions.</italic>
</bold>
 Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.</p>
</abstract>
<kwd-group>
<kwd>MERS-CoV Vaccine Design</kwd>
<kwd>Diagnostics</kwd>
<kwd>Serology</kwd>
<kwd>Synthetic Genomics</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region>
<li>Tennessee</li>
</region>
</list>
<tree>
<noCountry>
<name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name>
<name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name>
<name sortKey="Donaldson, Eric F" sort="Donaldson, Eric F" uniqKey="Donaldson E" first="Eric F." last="Donaldson">Eric F. Donaldson</name>
<name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L." last="Graham">Rachel L. Graham</name>
<name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E." last="Gralinski">Lisa E. Gralinski</name>
<name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D." last="Menachery">Vineet D. Menachery</name>
<name sortKey="Scobey, Trevor D" sort="Scobey, Trevor D" uniqKey="Scobey T" first="Trevor D." last="Scobey">Trevor D. Scobey</name>
<name sortKey="Yount, Boyd L" sort="Yount, Boyd L" uniqKey="Yount B" first="Boyd L." last="Yount">Boyd L. Yount</name>
</noCountry>
<country name="Royaume-Uni">
<noRegion>
<name sortKey="Gopal, Robin" sort="Gopal, Robin" uniqKey="Gopal R" first="Robin" last="Gopal">Robin Gopal</name>
</noRegion>
<name sortKey="Zambon, Maria" sort="Zambon, Maria" uniqKey="Zambon M" first="Maria" last="Zambon">Maria Zambon</name>
</country>
<country name="États-Unis">
<region name="Tennessee">
<name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name>
</region>
</country>
</tree>
</affiliations>
</record>

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Data generation: Tue Apr 28 14:49:16 2020. Site generation: Sat Mar 27 22:06:49 2021