MersV1, Main, Exploration, bibRecord, 000D46

Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen.

Identifieur interne : 000D46 ( Main/Exploration ); précédent : 000D45; suivant : 000D47

Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen.

Auteurs : Jesper Pallesen [États-Unis] ; Nianshuang Wang [États-Unis] ; Kizzmekia S. Corbett [États-Unis] ; Daniel Wrapp [États-Unis] ; Robert N. Kirchdoerfer [États-Unis] ; Hannah L. Turner [États-Unis] ; Christopher A. Cottrell [États-Unis] ; Michelle M. Becker [États-Unis] ; Lingshu Wang [États-Unis] ; Wei Shi [États-Unis] ; Wing-Pui Kong [États-Unis] ; Erica L. Andres [États-Unis] ; Arminja N. Kettenbach [États-Unis] ; Mark R. Denison [États-Unis] ; James D. Chappell [États-Unis] ; Barney S. Graham [États-Unis] ; Andrew B. Ward [États-Unis] ; Jason S. Mclellan [États-Unis]

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2017.

RBID : pubmed:28807998

Descripteurs français

English descriptors

KwdEn :
- Animals, Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Coronaviridae (immunology), Coronavirus Infections (virology), Crystallography, X-Ray (methods), Humans, Immunity, Humoral (immunology), Immunoglobulin G (metabolism), Mice, Inbred BALB C, Middle East Respiratory Syndrome Coronavirus (immunology), Protein Binding, Protein Conformation, Receptors, Virus (metabolism), Spike Glycoprotein, Coronavirus (immunology), Structure-Activity Relationship, Vaccination, Viral Vaccines (immunology).
MESH :
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Spike Glycoprotein, Coronavirus, Viral Vaccines.
- immunology : Coronaviridae, Immunity, Humoral, Middle East Respiratory Syndrome Coronavirus.
- chemical , metabolism : Immunoglobulin G, Receptors, Virus.
- methods : Crystallography, X-Ray.
- virology : Coronavirus Infections.
- Animals, Humans, Mice, Inbred BALB C, Protein Binding, Protein Conformation, Structure-Activity Relationship, Vaccination.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.

DOI: 10.1073/pnas.1707304114
PubMed: 28807998

Affiliations:

Le document en format XML

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<author><name sortKey="Wang, Lingshu" sort="Wang, Lingshu" uniqKey="Wang L" first="Lingshu" last="Wang">Lingshu Wang</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen.</title>
<author><name sortKey="Pallesen, Jesper" sort="Pallesen, Jesper" uniqKey="Pallesen J" first="Jesper" last="Pallesen">Jesper Pallesen</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla</wicri:cityArea>
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<author><name sortKey="Wang, Nianshuang" sort="Wang, Nianshuang" uniqKey="Wang N" first="Nianshuang" last="Wang">Nianshuang Wang</name>
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<author><name sortKey="Corbett, Kizzmekia S" sort="Corbett, Kizzmekia S" uniqKey="Corbett K" first="Kizzmekia S" last="Corbett">Kizzmekia S. Corbett</name>
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<placeName><region type="state">Maryland</region>
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<author><name sortKey="Wrapp, Daniel" sort="Wrapp, Daniel" uniqKey="Wrapp D" first="Daniel" last="Wrapp">Daniel Wrapp</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">New Hampshire</region>
</placeName>
<wicri:cityArea>Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover</wicri:cityArea>
</affiliation>
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<author><name sortKey="Kirchdoerfer, Robert N" sort="Kirchdoerfer, Robert N" uniqKey="Kirchdoerfer R" first="Robert N" last="Kirchdoerfer">Robert N. Kirchdoerfer</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla</wicri:cityArea>
</affiliation>
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<author><name sortKey="Turner, Hannah L" sort="Turner, Hannah L" uniqKey="Turner H" first="Hannah L" last="Turner">Hannah L. Turner</name>
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<placeName><region type="state">Californie</region>
</placeName>
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<author><name sortKey="Cottrell, Christopher A" sort="Cottrell, Christopher A" uniqKey="Cottrell C" first="Christopher A" last="Cottrell">Christopher A. Cottrell</name>
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<placeName><region type="state">Californie</region>
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<author><name sortKey="Becker, Michelle M" sort="Becker, Michelle M" uniqKey="Becker M" first="Michelle M" last="Becker">Michelle M. Becker</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Wang, Lingshu" sort="Wang, Lingshu" uniqKey="Wang L" first="Lingshu" last="Wang">Lingshu Wang</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
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</affiliation>
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<author><name sortKey="Shi, Wei" sort="Shi, Wei" uniqKey="Shi W" first="Wei" last="Shi">Wei Shi</name>
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<placeName><region type="state">Maryland</region>
</placeName>
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</affiliation>
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<author><name sortKey="Kong, Wing Pui" sort="Kong, Wing Pui" uniqKey="Kong W" first="Wing-Pui" last="Kong">Wing-Pui Kong</name>
<affiliation wicri:level="2"><nlm:affiliation>Virology Core, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Virology Core, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Andres, Erica L" sort="Andres, Erica L" uniqKey="Andres E" first="Erica L" last="Andres">Erica L. Andres</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kettenbach, Arminja N" sort="Kettenbach, Arminja N" uniqKey="Kettenbach A" first="Arminja N" last="Kettenbach">Arminja N. Kettenbach</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">New Hampshire</region>
</placeName>
<wicri:cityArea>Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover</wicri:cityArea>
</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"><nlm:affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Chappell, James D" sort="Chappell, James D" uniqKey="Chappell J" first="James D" last="Chappell">James D. Chappell</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S" last="Graham">Barney S. Graham</name>
<affiliation wicri:level="2"><nlm:affiliation>Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ward, Andrew B" sort="Ward, Andrew B" uniqKey="Ward A" first="Andrew B" last="Ward">Andrew B. Ward</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037; Nianshuang.Wang@dartmouth.edu andrew@scripps.edu Jason.S.McLellan@Dartmouth.edu.</nlm:affiliation>
<country wicri:rule="url">États-Unis</country>
<wicri:regionArea>Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla</wicri:regionArea>
<wicri:noRegion>La Jolla</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mclellan, Jason S" sort="Mclellan, Jason S" uniqKey="Mclellan J" first="Jason S" last="Mclellan">Jason S. Mclellan</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755; Nianshuang.Wang@dartmouth.edu andrew@scripps.edu Jason.S.McLellan@Dartmouth.edu.</nlm:affiliation>
<country wicri:rule="url">États-Unis</country>
<wicri:regionArea>Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover</wicri:regionArea>
<wicri:noRegion>Hanover</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2017" type="published">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antibodies, Neutralizing (immunology)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Coronaviridae (immunology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Crystallography, X-Ray (methods)</term>
<term>Humans</term>
<term>Immunity, Humoral (immunology)</term>
<term>Immunoglobulin G (metabolism)</term>
<term>Mice, Inbred BALB C</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Protein Binding</term>
<term>Protein Conformation</term>
<term>Receptors, Virus (metabolism)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>Structure-Activity Relationship</term>
<term>Vaccination</term>
<term>Viral Vaccines (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps neutralisants (immunologie)</term>
<term>Conformation des protéines</term>
<term>Coronaviridae (immunologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Cristallographie aux rayons X ()</term>
<term>Glycoprotéine de spicule des coronavirus (immunologie)</term>
<term>Humains</term>
<term>Immunité humorale (immunologie)</term>
<term>Immunoglobuline G (métabolisme)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Liaison aux protéines</term>
<term>Relation structure-activité</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Souris de lignée BALB C</term>
<term>Vaccination</term>
<term>Vaccins antiviraux (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</term>
<term>Coronaviridae</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Immunité humorale</term>
<term>Vaccins antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronaviridae</term>
<term>Immunity, Humoral</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Immunoglobulin G</term>
<term>Receptors, Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Crystallography, X-Ray</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Immunoglobuline G</term>
<term>Récepteurs viraux</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Humans</term>
<term>Mice, Inbred BALB C</term>
<term>Protein Binding</term>
<term>Protein Conformation</term>
<term>Structure-Activity Relationship</term>
<term>Vaccination</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Conformation des protéines</term>
<term>Cristallographie aux rayons X</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Relation structure-activité</term>
<term>Souris de lignée BALB C</term>
<term>Vaccination</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.</div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Maryland</li>
<li>New Hampshire</li>
<li>Tennessee</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Californie"><name sortKey="Pallesen, Jesper" sort="Pallesen, Jesper" uniqKey="Pallesen J" first="Jesper" last="Pallesen">Jesper Pallesen</name>
</region>
<name sortKey="Andres, Erica L" sort="Andres, Erica L" uniqKey="Andres E" first="Erica L" last="Andres">Erica L. Andres</name>
<name sortKey="Becker, Michelle M" sort="Becker, Michelle M" uniqKey="Becker M" first="Michelle M" last="Becker">Michelle M. Becker</name>
<name sortKey="Chappell, James D" sort="Chappell, James D" uniqKey="Chappell J" first="James D" last="Chappell">James D. Chappell</name>
<name sortKey="Corbett, Kizzmekia S" sort="Corbett, Kizzmekia S" uniqKey="Corbett K" first="Kizzmekia S" last="Corbett">Kizzmekia S. Corbett</name>
<name sortKey="Cottrell, Christopher A" sort="Cottrell, Christopher A" uniqKey="Cottrell C" first="Christopher A" last="Cottrell">Christopher A. Cottrell</name>
<name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R" last="Denison">Mark R. Denison</name>
<name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S" last="Graham">Barney S. Graham</name>
<name sortKey="Kettenbach, Arminja N" sort="Kettenbach, Arminja N" uniqKey="Kettenbach A" first="Arminja N" last="Kettenbach">Arminja N. Kettenbach</name>
<name sortKey="Kirchdoerfer, Robert N" sort="Kirchdoerfer, Robert N" uniqKey="Kirchdoerfer R" first="Robert N" last="Kirchdoerfer">Robert N. Kirchdoerfer</name>
<name sortKey="Kong, Wing Pui" sort="Kong, Wing Pui" uniqKey="Kong W" first="Wing-Pui" last="Kong">Wing-Pui Kong</name>
<name sortKey="Mclellan, Jason S" sort="Mclellan, Jason S" uniqKey="Mclellan J" first="Jason S" last="Mclellan">Jason S. Mclellan</name>
<name sortKey="Shi, Wei" sort="Shi, Wei" uniqKey="Shi W" first="Wei" last="Shi">Wei Shi</name>
<name sortKey="Turner, Hannah L" sort="Turner, Hannah L" uniqKey="Turner H" first="Hannah L" last="Turner">Hannah L. Turner</name>
<name sortKey="Wang, Lingshu" sort="Wang, Lingshu" uniqKey="Wang L" first="Lingshu" last="Wang">Lingshu Wang</name>
<name sortKey="Wang, Nianshuang" sort="Wang, Nianshuang" uniqKey="Wang N" first="Nianshuang" last="Wang">Nianshuang Wang</name>
<name sortKey="Ward, Andrew B" sort="Ward, Andrew B" uniqKey="Ward A" first="Andrew B" last="Ward">Andrew B. Ward</name>
<name sortKey="Wrapp, Daniel" sort="Wrapp, Daniel" uniqKey="Wrapp D" first="Daniel" last="Wrapp">Daniel Wrapp</name>
</country>
</tree>
</affiliations>
</record>

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Serveur d'exploration MERS

Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen.

Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen.

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