Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein
Identifieur interne : 000337 ( Main/Exploration ); précédent : 000336; suivant : 000338Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein
Auteurs : Ivy Widjaja [Pays-Bas] ; Chunyan Wang [Pays-Bas] ; Rien Van Haperen [Pays-Bas] ; Javier Gutiérrez-Álvarez [Espagne] ; Brenda Van Dieren [Pays-Bas] ; Nisreen M. A. Okba [Pays-Bas] ; V. Stalin Raj [Pays-Bas] ; Wentao Li [Pays-Bas] ; Raul Fernandez-Delgado [Espagne] ; Frank Grosveld [Pays-Bas] ; Frank J. M. Van Kuppeveld [Pays-Bas] ; Bart L. Haagmans [Pays-Bas] ; Luis Enjuanes [Espagne] ; Dubravka Drabek [Pays-Bas] ; Berend-Jan Bosch [Pays-Bas]Source :
- Emerging Microbes & Infections [ 2222-1751 ] ; 2019.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps monoclonaux (immunologie), Anticorps neutralisants (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (génétique), Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Domaines protéiques, Glycoprotéine de spicule des coronavirus (), Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (immunologie), Humains, Immunisation passive, Infections à coronavirus (), Infections à coronavirus (génétique), Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Récepteurs viraux (génétique), Récepteurs viraux (immunologie), Souris, Épitopes (), Épitopes (génétique), Épitopes (immunologie).
- MESH :
- génétique : Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Infections à coronavirus, Récepteurs viraux, Épitopes.
- immunologie : Anticorps antiviraux, Anticorps monoclonaux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Infections à coronavirus, Récepteurs viraux, Épitopes.
- virologie : Infections à coronavirus.
- Animaux, Coronavirus du syndrome respiratoire du Moyen-Orient, Domaines protéiques, Glycoprotéine de spicule des coronavirus, Humains, Immunisation passive, Infections à coronavirus, Souris, Épitopes.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (immunology), Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Coronavirus Infections (genetics), Coronavirus Infections (immunology), Coronavirus Infections (prevention & control), Coronavirus Infections (virology), Epitopes (chemistry), Epitopes (genetics), Epitopes (immunology), Humans, Immunization, Passive, Mice, Middle East Respiratory Syndrome Coronavirus (chemistry), Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (immunology), Protein Domains, Receptors, Virus (genetics), Receptors, Virus (immunology), Spike Glycoprotein, Coronavirus (chemistry), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology).
- MESH :
- chemical , chemistry : Epitopes, Spike Glycoprotein, Coronavirus.
- chemical , genetics : Epitopes, Receptors, Virus, Spike Glycoprotein, Coronavirus.
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Epitopes, Receptors, Virus, Spike Glycoprotein, Coronavirus.
- chemistry : Middle East Respiratory Syndrome Coronavirus.
- genetics : Coronavirus Infections, Middle East Respiratory Syndrome Coronavirus.
- immunology : Coronavirus Infections, Middle East Respiratory Syndrome Coronavirus.
- prevention & control : Coronavirus Infections.
- virology : Coronavirus Infections.
- Animals, Humans, Immunization, Passive, Mice, Protein Domains.
Abstract
The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.
Url:
DOI: 10.1080/22221751.2019.1597644
PubMed: 30938227
PubMed Central: 6455120
Affiliations:
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Le document en format XML
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<author><name sortKey="Widjaja, Ivy" sort="Widjaja, Ivy" uniqKey="Widjaja I" first="Ivy" last="Widjaja">Ivy Widjaja</name>
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<author><name sortKey="Raj, V Stalin" sort="Raj, V Stalin" uniqKey="Raj V" first="V. Stalin" last="Raj">V. Stalin Raj</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L." last="Haagmans">Bart L. Haagmans</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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, Madrid,<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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, Rotterdam,<country>Netherlands</country>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="AF3"><institution>Harbour Antibodies B.V.</institution>
, Rotterdam,<country>Netherlands</country>
</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bosch, Berend Jan" sort="Bosch, Berend Jan" uniqKey="Bosch B" first="Berend-Jan" last="Bosch">Berend-Jan Bosch</name>
<affiliation wicri:level="1"><nlm:aff id="AF1"><institution>Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University</institution>
, Utrecht,<country>Netherlands</country>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Emerging Microbes & Infections</title>
<idno type="eISSN">2222-1751</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antibodies, Monoclonal (immunology)</term>
<term>Antibodies, Neutralizing (immunology)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Coronavirus Infections (genetics)</term>
<term>Coronavirus Infections (immunology)</term>
<term>Coronavirus Infections (prevention & control)</term>
<term>Coronavirus Infections (virology)</term>
<term>Epitopes (chemistry)</term>
<term>Epitopes (genetics)</term>
<term>Epitopes (immunology)</term>
<term>Humans</term>
<term>Immunization, Passive</term>
<term>Mice</term>
<term>Middle East Respiratory Syndrome Coronavirus (chemistry)</term>
<term>Middle East Respiratory Syndrome Coronavirus (genetics)</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Protein Domains</term>
<term>Receptors, Virus (genetics)</term>
<term>Receptors, Virus (immunology)</term>
<term>Spike Glycoprotein, Coronavirus (chemistry)</term>
<term>Spike Glycoprotein, Coronavirus (genetics)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps monoclonaux (immunologie)</term>
<term>Anticorps neutralisants (immunologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Domaines protéiques</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>Immunisation passive</term>
<term>Infections à coronavirus ()</term>
<term>Infections à coronavirus (génétique)</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Récepteurs viraux (génétique)</term>
<term>Récepteurs viraux (immunologie)</term>
<term>Souris</term>
<term>Épitopes ()</term>
<term>Épitopes (génétique)</term>
<term>Épitopes (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Epitopes</term>
<term>Receptors, Virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
<term>Epitopes</term>
<term>Receptors, Virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronavirus Infections</term>
<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>Glycoprotéine de spicule des coronavirus</term>
<term>Infections à coronavirus</term>
<term>Récepteurs viraux</term>
<term>Épitopes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux</term>
<term>Anticorps neutralisants</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Infections à coronavirus</term>
<term>Récepteurs viraux</term>
<term>Épitopes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Middle East Respiratory Syndrome Coronavirus</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>Humans</term>
<term>Immunization, Passive</term>
<term>Mice</term>
<term>Protein Domains</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Domaines protéiques</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Immunisation passive</term>
<term>Infections à coronavirus</term>
<term>Souris</term>
<term>Épitopes</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.</p>
</div>
</front>
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</biblStruct>
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</div1>
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</TEI>
<affiliations><list><country><li>Espagne</li>
<li>Pays-Bas</li>
</country>
</list>
<tree><country name="Pays-Bas"><noRegion><name sortKey="Widjaja, Ivy" sort="Widjaja, Ivy" uniqKey="Widjaja I" first="Ivy" last="Widjaja">Ivy Widjaja</name>
</noRegion>
<name sortKey="Bosch, Berend Jan" sort="Bosch, Berend Jan" uniqKey="Bosch B" first="Berend-Jan" last="Bosch">Berend-Jan Bosch</name>
<name sortKey="Drabek, Dubravka" sort="Drabek, Dubravka" uniqKey="Drabek D" first="Dubravka" last="Drabek">Dubravka Drabek</name>
<name sortKey="Drabek, Dubravka" sort="Drabek, Dubravka" uniqKey="Drabek D" first="Dubravka" last="Drabek">Dubravka Drabek</name>
<name sortKey="Grosveld, Frank" sort="Grosveld, Frank" uniqKey="Grosveld F" first="Frank" last="Grosveld">Frank Grosveld</name>
<name sortKey="Grosveld, Frank" sort="Grosveld, Frank" uniqKey="Grosveld F" first="Frank" last="Grosveld">Frank Grosveld</name>
<name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L." last="Haagmans">Bart L. Haagmans</name>
<name sortKey="Li, Wentao" sort="Li, Wentao" uniqKey="Li W" first="Wentao" last="Li">Wentao Li</name>
<name sortKey="Okba, Nisreen M A" sort="Okba, Nisreen M A" uniqKey="Okba N" first="Nisreen M. A." last="Okba">Nisreen M. A. Okba</name>
<name sortKey="Raj, V Stalin" sort="Raj, V Stalin" uniqKey="Raj V" first="V. Stalin" last="Raj">V. Stalin Raj</name>
<name sortKey="Van Dieren, Brenda" sort="Van Dieren, Brenda" uniqKey="Van Dieren B" first="Brenda" last="Van Dieren">Brenda Van Dieren</name>
<name sortKey="Van Haperen, Rien" sort="Van Haperen, Rien" uniqKey="Van Haperen R" first="Rien" last="Van Haperen">Rien Van Haperen</name>
<name sortKey="Van Haperen, Rien" sort="Van Haperen, Rien" uniqKey="Van Haperen R" first="Rien" last="Van Haperen">Rien Van Haperen</name>
<name sortKey="Van Kuppeveld, Frank J M" sort="Van Kuppeveld, Frank J M" uniqKey="Van Kuppeveld F" first="Frank J. M." last="Van Kuppeveld">Frank J. M. Van Kuppeveld</name>
<name sortKey="Wang, Chunyan" sort="Wang, Chunyan" uniqKey="Wang C" first="Chunyan" last="Wang">Chunyan Wang</name>
</country>
<country name="Espagne"><noRegion><name sortKey="Gutierrez Lvarez, Javier" sort="Gutierrez Lvarez, Javier" uniqKey="Gutierrez Lvarez J" first="Javier" last="Gutiérrez-Álvarez">Javier Gutiérrez-Álvarez</name>
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<name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name>
<name sortKey="Fernandez Delgado, Raul" sort="Fernandez Delgado, Raul" uniqKey="Fernandez Delgado R" first="Raul" last="Fernandez-Delgado">Raul Fernandez-Delgado</name>
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</record>
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