Serveur d'exploration MERS

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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 : 001E51 ( Main/Exploration ); précédent : 001E50; suivant : 001E52

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

Source :

RBID : Pascal:14-0109853

Descripteurs français

English descriptors

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.


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<title xml:lang="en" level="a">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</title>
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<name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L." last="Graham">Rachel L. Graham</name>
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<s1>Department of Epidemiology, University of North Carolina</s1>
<s2>Chapel Hill</s2>
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<country>États-Unis</country>
<wicri:noRegion>Chapel Hill</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<inist:fA14 i1="02">
<s1>Department of Microbiology and Immunology, University of North Carolina</s1>
<s2>Chapel Hill</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<wicri:noRegion>Chapel Hill</wicri:noRegion>
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<author>
<name sortKey="Scobey, Trevor D" sort="Scobey, Trevor D" uniqKey="Scobey T" first="Trevor D." last="Scobey">Trevor D. Scobey</name>
<affiliation wicri:level="1">
<inist:fA14 i1="01">
<s1>Department of Epidemiology, University of North Carolina</s1>
<s2>Chapel Hill</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<wicri:noRegion>Chapel Hill</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<inist:fA14 i1="02">
<s1>Department of Microbiology and Immunology, University of North Carolina</s1>
<s2>Chapel Hill</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<wicri:noRegion>Chapel Hill</wicri:noRegion>
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</author>
<author>
<name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E." last="Gralinski">Lisa E. Gralinski</name>
<affiliation wicri:level="1">
<inist:fA14 i1="01">
<s1>Department of Epidemiology, University of North Carolina</s1>
<s2>Chapel Hill</s2>
<s3>USA</s3>
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</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Chapel Hill</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<inist:fA14 i1="02">
<s1>Department of Microbiology and Immunology, University of North Carolina</s1>
<s2>Chapel Hill</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<wicri:noRegion>Chapel Hill</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name>
<affiliation wicri:level="2">
<inist:fA14 i1="03">
<s1>Departments of Pediatrics and Microbiology and Immunology, Vanderbilt University</s1>
<s2>Nashville, Tennessee</s2>
<s3>USA</s3>
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</inist:fA14>
<country>États-Unis</country>
<placeName>
<region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Zambon, Maria" sort="Zambon, Maria" uniqKey="Zambon M" first="Maria" last="Zambon">Maria Zambon</name>
<affiliation wicri:level="3">
<inist:fA14 i1="04">
<s1>Viral Zoonosis Unit, Public Health of England</s1>
<s2>London</s2>
<s3>GBR</s3>
<sZ>2 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</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 wicri:level="1">
<inist:fA14 i1="01">
<s1>Department of Epidemiology, University of North Carolina</s1>
<s2>Chapel Hill</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Chapel Hill</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<inist:fA14 i1="02">
<s1>Department of Microbiology and Immunology, University of North Carolina</s1>
<s2>Chapel Hill</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Chapel Hill</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j" type="main">The Journal of infectious diseases</title>
<title level="j" type="abbreviated">J. infect. dis.</title>
<idno type="ISSN">0022-1899</idno>
<imprint>
<date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<title level="j" type="main">The Journal of infectious diseases</title>
<title level="j" type="abbreviated">J. infect. dis.</title>
<idno type="ISSN">0022-1899</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Coronavirus</term>
<term>Infection</term>
<term>Serology</term>
<term>Vaccine</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Coronavirus</term>
<term>Sérologie</term>
<term>Vaccin</term>
<term>Infection</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Vaccin</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">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.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region>
<li>Angleterre</li>
<li>Grand Londres</li>
<li>Tennessee</li>
</region>
<settlement>
<li>Londres</li>
</settlement>
</list>
<tree>
<country name="États-Unis">
<noRegion>
<name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name>
</noRegion>
<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="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name>
<name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name>
<name sortKey="Donaldson, Eric F" sort="Donaldson, Eric F" uniqKey="Donaldson E" first="Eric F." last="Donaldson">Eric F. Donaldson</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="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="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="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="Scobey, Trevor D" sort="Scobey, Trevor D" uniqKey="Scobey T" first="Trevor D." last="Scobey">Trevor D. Scobey</name>
<name sortKey="Yount, Boyd L Jr" sort="Yount, Boyd L Jr" uniqKey="Yount B" first="Boyd L. Jr" last="Yount">Boyd L. Jr Yount</name>
<name sortKey="Yount, Boyd L Jr" sort="Yount, Boyd L Jr" uniqKey="Yount B" first="Boyd L. Jr" last="Yount">Boyd L. Jr Yount</name>
</country>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Gopal, Robin" sort="Gopal, Robin" uniqKey="Gopal R" first="Robin" last="Gopal">Robin Gopal</name>
</region>
<name sortKey="Zambon, Maria" sort="Zambon, Maria" uniqKey="Zambon M" first="Maria" last="Zambon">Maria Zambon</name>
</country>
</tree>
</affiliations>
</record>

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