MersV1, Main, Exploration, bibRecord, 000C13

Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants.

Identifieur interne : 000C13 ( Main/Exploration ); précédent : 000C12; suivant : 000C14

Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants.

Auteurs : Wanbo Tai [États-Unis] ; Yufei Wang [États-Unis] ; Craig A. Fett [États-Unis] ; Guangyu Zhao [République populaire de Chine] ; Fang Li [États-Unis] ; Stanley Perlman [États-Unis] ; Shibo Jiang [États-Unis] ; Yusen Zhou [République populaire de Chine] ; Lanying Du [République populaire de Chine]

Source :

Journal of virology [ 1098-5514 ] ; 2017.

RBID : pubmed:27795425

Descripteurs français

English descriptors

KwdEn :
- Animals, Antibodies, Neutralizing (biosynthesis), Antibodies, Neutralizing (chemistry), Antibodies, Viral (biosynthesis), Antibodies, Viral (chemistry), Binding Sites, Camelus, Coronavirus Infections (immunology), Coronavirus Infections (prevention & control), Coronavirus Infections (virology), Cross Reactions, Dipeptidyl Peptidase 4 (chemistry), Dipeptidyl Peptidase 4 (genetics), Dipeptidyl Peptidase 4 (immunology), Female, Gene Expression, Humans, Immune Evasion, Mice, Mice, Inbred BALB C, Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (immunology), Models, Molecular, Mutation, Neutralization Tests, Plasmids (chemistry), Plasmids (metabolism), Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Receptors, Virus (chemistry), Receptors, Virus (genetics), Receptors, Virus (immunology), Recombinant Proteins (chemistry), Recombinant Proteins (genetics), Recombinant Proteins (immunology), Spike Glycoprotein, Coronavirus (chemistry), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology), Vaccination, Viral Vaccines (administration & dosage), Viral Vaccines (biosynthesis).
MESH :
- chemical , administration & dosage : Viral Vaccines.
- chemical , biosynthesis : Antibodies, Neutralizing, Antibodies, Viral, Viral Vaccines.
- chemical , chemistry : Antibodies, Neutralizing, Antibodies, Viral, Dipeptidyl Peptidase 4, Receptors, Virus, Recombinant Proteins, Spike Glycoprotein, Coronavirus.
- chemical , genetics : Dipeptidyl Peptidase 4, Receptors, Virus, Recombinant Proteins, Spike Glycoprotein, Coronavirus.
- chemistry : Plasmids.
- genetics : Middle East Respiratory Syndrome Coronavirus.
- immunology : Coronavirus Infections, Dipeptidyl Peptidase 4, Middle East Respiratory Syndrome Coronavirus, Receptors, Virus, Recombinant Proteins, Spike Glycoprotein, Coronavirus.
- metabolism : Plasmids.
- prevention & control : Coronavirus Infections.
- virology : Coronavirus Infections.
- Animals, Binding Sites, Camelus, Cross Reactions, Female, Gene Expression, Humans, Immune Evasion, Mice, Mice, Inbred BALB C, Models, Molecular, Mutation, Neutralization Tests, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Vaccination.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via the spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014, and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains. Like the RBD of prototype EMC2012 (EMC-RBD), all five RBDs maintained good antigenicity and functionality, the ability to bind RBD-specific neutralizing monoclonal antibodies (MAbs) and the DPP4 receptor, and high immunogenicity, able to elicit S-specific antibodies. They induced potent neutralizing antibodies cross-neutralizing 17 MERS pseudoviruses expressing S proteins of representative human and camel MERS-CoV strains identified during the 2012-2015 outbreaks, 5 MAb escape MERS-CoV mutants, and 2 live human MERS-CoV strains. We then constructed two RBDs mutated in multiple key residues in the receptor-binding motif (RBM) of RBD and demonstrated their strong cross-reactivity with anti-EMC-RBD antibodies. These RBD mutants with diminished DPP4 binding also led to virus attenuation, suggesting that immunoevasion after RBD immunization is accompanied by loss of viral fitness. Therefore, this study demonstrates that MERS-CoV RBD is an important vaccine target able to induce highly potent and broad-spectrum neutralizing antibodies against infection by divergent circulating human and camel MERS-CoV strains.

DOI: 10.1128/JVI.01651-16
PubMed: 27795425

Affiliations:

Le document en format XML

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<term>Antibodies, Neutralizing (biosynthesis)</term>
<term>Antibodies, Neutralizing (chemistry)</term>
<term>Antibodies, Viral (biosynthesis)</term>
<term>Antibodies, Viral (chemistry)</term>
<term>Binding Sites</term>
<term>Camelus</term>
<term>Coronavirus Infections (immunology)</term>
<term>Coronavirus Infections (prevention & control)</term>
<term>Coronavirus Infections (virology)</term>
<term>Cross Reactions</term>
<term>Dipeptidyl Peptidase 4 (chemistry)</term>
<term>Dipeptidyl Peptidase 4 (genetics)</term>
<term>Dipeptidyl Peptidase 4 (immunology)</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Immune Evasion</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Middle East Respiratory Syndrome Coronavirus (genetics)</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Models, Molecular</term>
<term>Mutation</term>
<term>Neutralization Tests</term>
<term>Plasmids (chemistry)</term>
<term>Plasmids (metabolism)</term>
<term>Protein Binding</term>
<term>Protein Interaction Domains and Motifs</term>
<term>Protein Structure, Secondary</term>
<term>Receptors, Virus (chemistry)</term>
<term>Receptors, Virus (genetics)</term>
<term>Receptors, Virus (immunology)</term>
<term>Recombinant Proteins (chemistry)</term>
<term>Recombinant Proteins (genetics)</term>
<term>Recombinant Proteins (immunology)</term>
<term>Spike Glycoprotein, Coronavirus (chemistry)</term>
<term>Spike Glycoprotein, Coronavirus (genetics)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>Vaccination</term>
<term>Viral Vaccines (administration & dosage)</term>
<term>Viral Vaccines (biosynthesis)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Anticorps antiviraux ()</term>
<term>Anticorps antiviraux (biosynthèse)</term>
<term>Anticorps neutralisants ()</term>
<term>Anticorps neutralisants (biosynthèse)</term>
<term>Chameaux</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Dipeptidyl peptidase 4 ()</term>
<term>Dipeptidyl peptidase 4 (génétique)</term>
<term>Dipeptidyl peptidase 4 (immunologie)</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus ()</term>
<term>Glycoprotéine de spicule des coronavirus (génétique)</term>
<term>Glycoprotéine de spicule des coronavirus (immunologie)</term>
<term>Humains</term>
<term>Infections à coronavirus ()</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Liaison aux protéines</term>
<term>Modèles moléculaires</term>
<term>Motifs et domaines d'intéraction protéique</term>
<term>Mutation</term>
<term>Plasmides ()</term>
<term>Plasmides (métabolisme)</term>
<term>Protéines recombinantes ()</term>
<term>Protéines recombinantes (génétique)</term>
<term>Protéines recombinantes (immunologie)</term>
<term>Réactions croisées</term>
<term>Récepteurs viraux ()</term>
<term>Récepteurs viraux (génétique)</term>
<term>Récepteurs viraux (immunologie)</term>
<term>Sites de fixation</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Structure secondaire des protéines</term>
<term>Tests de neutralisation</term>
<term>Vaccination</term>
<term>Vaccins antiviraux (administration et posologie)</term>
<term>Vaccins antiviraux (biosynthèse)</term>
<term>Échappement immunitaire</term>
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<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
<term>Dipeptidyl Peptidase 4</term>
<term>Receptors, Virus</term>
<term>Recombinant Proteins</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dipeptidyl Peptidase 4</term>
<term>Receptors, Virus</term>
<term>Recombinant Proteins</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vaccins antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</term>
<term>Vaccins antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Plasmids</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Dipeptidyl peptidase 4</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Protéines recombinantes</term>
<term>Récepteurs viraux</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Dipeptidyl peptidase 4</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Infections à coronavirus</term>
<term>Protéines recombinantes</term>
<term>Récepteurs viraux</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Dipeptidyl Peptidase 4</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Receptors, Virus</term>
<term>Recombinant Proteins</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Plasmids</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Plasmides</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</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>Binding Sites</term>
<term>Camelus</term>
<term>Cross Reactions</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Immune Evasion</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Models, Molecular</term>
<term>Mutation</term>
<term>Neutralization Tests</term>
<term>Protein Binding</term>
<term>Protein Interaction Domains and Motifs</term>
<term>Protein Structure, Secondary</term>
<term>Vaccination</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</term>
<term>Chameaux</term>
<term>Dipeptidyl peptidase 4</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Infections à coronavirus</term>
<term>Liaison aux protéines</term>
<term>Modèles moléculaires</term>
<term>Motifs et domaines d'intéraction protéique</term>
<term>Mutation</term>
<term>Plasmides</term>
<term>Protéines recombinantes</term>
<term>Réactions croisées</term>
<term>Récepteurs viraux</term>
<term>Sites de fixation</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Structure secondaire des protéines</term>
<term>Tests de neutralisation</term>
<term>Vaccination</term>
<term>Échappement immunitaire</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via the spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014, and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains. Like the RBD of prototype EMC2012 (EMC-RBD), all five RBDs maintained good antigenicity and functionality, the ability to bind RBD-specific neutralizing monoclonal antibodies (MAbs) and the DPP4 receptor, and high immunogenicity, able to elicit S-specific antibodies. They induced potent neutralizing antibodies cross-neutralizing 17 MERS pseudoviruses expressing S proteins of representative human and camel MERS-CoV strains identified during the 2012-2015 outbreaks, 5 MAb escape MERS-CoV mutants, and 2 live human MERS-CoV strains. We then constructed two RBDs mutated in multiple key residues in the receptor-binding motif (RBM) of RBD and demonstrated their strong cross-reactivity with anti-EMC-RBD antibodies. These RBD mutants with diminished DPP4 binding also led to virus attenuation, suggesting that immunoevasion after RBD immunization is accompanied by loss of viral fitness. Therefore, this study demonstrates that MERS-CoV RBD is an important vaccine target able to induce highly potent and broad-spectrum neutralizing antibodies against infection by divergent circulating human and camel MERS-CoV strains.</div>
</front>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Iowa</li>
<li>Minnesota</li>
<li>État de New York</li>
</region>
<settlement><li>Iowa City</li>
<li>Pékin</li>
</settlement>
<orgName><li>Université de l'Iowa</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="État de New York"><name sortKey="Tai, Wanbo" sort="Tai, Wanbo" uniqKey="Tai W" first="Wanbo" last="Tai">Wanbo Tai</name>
</region>
<name sortKey="Fett, Craig A" sort="Fett, Craig A" uniqKey="Fett C" first="Craig A" last="Fett">Craig A. Fett</name>
<name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
<name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name>
<name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<name sortKey="Wang, Yufei" sort="Wang, Yufei" uniqKey="Wang Y" first="Yufei" last="Wang">Yufei Wang</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name>
</noRegion>
<name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
<name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name>
</country>
</tree>
</affiliations>
</record>

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Serveur d'exploration MERS

Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants.

Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants.

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