MersV1, Main, Exploration, bibRecord, 001C29

Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution.

Identifieur interne : 001C29 ( Main/Exploration ); précédent : 001C28; suivant : 001C30

Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution.

Auteurs : Xian-Chun Tang [États-Unis] ; Sudhakar S. Agnihothram ; Yongjun Jiao [États-Unis] ; Jeremy Stanhope [États-Unis] ; Rachel L. Graham ; Eric C. Peterson [États-Unis] ; Yuval Avnir [États-Unis] ; Aimee St Clair Tallarico [États-Unis] ; Jared Sheehan [États-Unis] ; Quan Zhu [États-Unis] ; Ralph S. Baric [États-Unis] ; Wayne A. Marasco [États-Unis]

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2014.

RBID : pubmed:24778221

Descripteurs français

English descriptors

KwdEn :
- Amino Acid Sequence, Animals, Antibodies, Neutralizing (immunology), Antibodies, Neutralizing (isolation & purification), Antibodies, Viral (immunology), Antibodies, Viral (isolation & purification), Antiviral Agents (immunology), Antiviral Agents (isolation & purification), Biological Evolution, Communicable Diseases, Emerging (drug therapy), Communicable Diseases, Emerging (immunology), Communicable Diseases, Emerging (mortality), Coronavirus (genetics), Coronavirus (immunology), Coronavirus Infections (drug therapy), Coronavirus Infections (immunology), Coronavirus Infections (mortality), Dipeptidyl Peptidase 4 (immunology), HEK293 Cells, Humans, Immunoglobulin G (immunology), Molecular Sequence Data, Phylogeny, Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology), Viral Vaccines (immunology), Zoonoses (drug therapy), Zoonoses (immunology), Zoonoses (mortality).
MESH :
- chemical , genetics : Spike Glycoprotein, Coronavirus.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Antiviral Agents, Dipeptidyl Peptidase 4, Immunoglobulin G, Spike Glycoprotein, Coronavirus, Viral Vaccines.
- chemical , isolation & purification : Antibodies, Neutralizing, Antibodies, Viral, Antiviral Agents.
- drug therapy : Communicable Diseases, Emerging, Coronavirus Infections, Zoonoses.
- genetics : Coronavirus.
- immunology : Communicable Diseases, Emerging, Coronavirus, Coronavirus Infections, Zoonoses.
- mortality : Communicable Diseases, Emerging, Coronavirus Infections, Zoonoses.
- Amino Acid Sequence, Animals, Biological Evolution, HEK293 Cells, Humans, Molecular Sequence Data, Phylogeny.

Abstract

The newly emerging Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a Severe Acute Respiratory Syndrome-like disease with ∼43% mortality. Given the recent detection of virus in dromedary camels, zoonotic transfer of MERS-CoV to humans is suspected. In addition, little is known about the role of human neutralizing Ab (nAb) pressure as a driving force in MERS-CoV adaptive evolution. Here, we used a well-characterized nonimmune human Ab-phage library and a panning strategy with proteoliposomes and cells to identify seven human nAbs against the receptor-binding domain (RBD) of the MERS-CoV Spike protein. These nAbs bind to three different epitopes in the RBD and human dipeptidyl peptidase 4 (hDPP4) interface with subnanomolar/nanomolar binding affinities and block the binding of MERS-CoV Spike protein with its hDPP4 receptor. Escape mutant assays identified five amino acid residues that are critical for neutralization escape. Despite the close proximity of the three epitopes on the RBD interface, escape from one epitope did not have a major impact on neutralization with Abs directed to a different epitope. Importantly, the majority of escape mutations had negative impacts on hDPP4 receptor binding and viral fitness. To our knowledge, these results provide the first report on human nAbs against MERS-CoV that may contribute to MERS-CoV clearance and evolution. Moreover, in the absence of a licensed vaccine or antiviral for MERS, this panel of nAbs offers the possibility of developing human mAb-based immunotherapy, especially for health-care workers.

DOI: 10.1073/pnas.1402074111
PubMed: 24778221

Affiliations:

Le document en format XML

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<author><name sortKey="Sheehan, Jared" sort="Sheehan, Jared" uniqKey="Sheehan J" first="Jared" last="Sheehan">Jared Sheehan</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
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</affiliation>
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<author><name sortKey="Zhu, Quan" sort="Zhu, Quan" uniqKey="Zhu Q" first="Quan" last="Zhu">Quan Zhu</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
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</affiliation>
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<author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name>
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<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
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<author><name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A" last="Marasco">Wayne A. Marasco</name>
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<term>Animals</term>
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<term>Antibodies, Neutralizing (isolation & purification)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Antibodies, Viral (isolation & purification)</term>
<term>Antiviral Agents (immunology)</term>
<term>Antiviral Agents (isolation & purification)</term>
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<term>Communicable Diseases, Emerging (drug therapy)</term>
<term>Communicable Diseases, Emerging (immunology)</term>
<term>Communicable Diseases, Emerging (mortality)</term>
<term>Coronavirus (genetics)</term>
<term>Coronavirus (immunology)</term>
<term>Coronavirus Infections (drug therapy)</term>
<term>Coronavirus Infections (immunology)</term>
<term>Coronavirus Infections (mortality)</term>
<term>Dipeptidyl Peptidase 4 (immunology)</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Immunoglobulin G (immunology)</term>
<term>Molecular Sequence Data</term>
<term>Phylogeny</term>
<term>Spike Glycoprotein, Coronavirus (genetics)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>Viral Vaccines (immunology)</term>
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<term>Anticorps neutralisants (isolement et purification)</term>
<term>Antiviraux (immunologie)</term>
<term>Antiviraux (isolement et purification)</term>
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<term>Coronavirus (génétique)</term>
<term>Coronavirus (immunologie)</term>
<term>Dipeptidyl peptidase 4 (immunologie)</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus (génétique)</term>
<term>Glycoprotéine de spicule des coronavirus (immunologie)</term>
<term>Humains</term>
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<term>Infections à coronavirus (traitement médicamenteux)</term>
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<term>Antibodies, Viral</term>
<term>Antiviral Agents</term>
<term>Dipeptidyl Peptidase 4</term>
<term>Immunoglobulin G</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Vaccines</term>
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<term>Antibodies, Viral</term>
<term>Antiviral Agents</term>
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<term>Coronavirus Infections</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronavirus</term>
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<term>Dipeptidyl peptidase 4</term>
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<term>Vaccins antiviraux</term>
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<term>Coronavirus</term>
<term>Coronavirus Infections</term>
<term>Zoonoses</term>
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<term>Anticorps neutralisants</term>
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<term>Coronavirus Infections</term>
<term>Zoonoses</term>
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<keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Maladies transmissibles émergentes</term>
<term>Zoonoses</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Maladies transmissibles émergentes</term>
<term>Zoonoses</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Biological Evolution</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
<term>Phylogeny</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules HEK293</term>
<term>Données de séquences moléculaires</term>
<term>Humains</term>
<term>Phylogénie</term>
<term>Séquence d'acides aminés</term>
<term>Évolution biologique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The newly emerging Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a Severe Acute Respiratory Syndrome-like disease with ∼43% mortality. Given the recent detection of virus in dromedary camels, zoonotic transfer of MERS-CoV to humans is suspected. In addition, little is known about the role of human neutralizing Ab (nAb) pressure as a driving force in MERS-CoV adaptive evolution. Here, we used a well-characterized nonimmune human Ab-phage library and a panning strategy with proteoliposomes and cells to identify seven human nAbs against the receptor-binding domain (RBD) of the MERS-CoV Spike protein. These nAbs bind to three different epitopes in the RBD and human dipeptidyl peptidase 4 (hDPP4) interface with subnanomolar/nanomolar binding affinities and block the binding of MERS-CoV Spike protein with its hDPP4 receptor. Escape mutant assays identified five amino acid residues that are critical for neutralization escape. Despite the close proximity of the three epitopes on the RBD interface, escape from one epitope did not have a major impact on neutralization with Abs directed to a different epitope. Importantly, the majority of escape mutations had negative impacts on hDPP4 receptor binding and viral fitness. To our knowledge, these results provide the first report on human nAbs against MERS-CoV that may contribute to MERS-CoV clearance and evolution. Moreover, in the absence of a licensed vaccine or antiviral for MERS, this panel of nAbs offers the possibility of developing human mAb-based immunotherapy, especially for health-care workers. </div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
<li>Massachusetts</li>
</region>
<settlement><li>Boston</li>
<li>Chapel Hill (Caroline du Nord)</li>
</settlement>
<orgName><li>Université de Caroline du Nord à Chapel Hill</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Agnihothram, Sudhakar S" sort="Agnihothram, Sudhakar S" uniqKey="Agnihothram S" first="Sudhakar S" last="Agnihothram">Sudhakar S. Agnihothram</name>
<name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L" last="Graham">Rachel L. Graham</name>
</noCountry>
<country name="États-Unis"><region name="Massachusetts"><name sortKey="Tang, Xian Chun" sort="Tang, Xian Chun" uniqKey="Tang X" first="Xian-Chun" last="Tang">Xian-Chun Tang</name>
</region>
<name sortKey="Avnir, Yuval" sort="Avnir, Yuval" uniqKey="Avnir Y" first="Yuval" last="Avnir">Yuval Avnir</name>
<name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name>
<name sortKey="Jiao, Yongjun" sort="Jiao, Yongjun" uniqKey="Jiao Y" first="Yongjun" last="Jiao">Yongjun Jiao</name>
<name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A" last="Marasco">Wayne A. Marasco</name>
<name sortKey="Peterson, Eric C" sort="Peterson, Eric C" uniqKey="Peterson E" first="Eric C" last="Peterson">Eric C. Peterson</name>
<name sortKey="Sheehan, Jared" sort="Sheehan, Jared" uniqKey="Sheehan J" first="Jared" last="Sheehan">Jared Sheehan</name>
<name sortKey="Stanhope, Jeremy" sort="Stanhope, Jeremy" uniqKey="Stanhope J" first="Jeremy" last="Stanhope">Jeremy Stanhope</name>
<name sortKey="Tallarico, Aimee St Clair" sort="Tallarico, Aimee St Clair" uniqKey="Tallarico A" first="Aimee St Clair" last="Tallarico">Aimee St Clair Tallarico</name>
<name sortKey="Zhu, Quan" sort="Zhu, Quan" uniqKey="Zhu Q" first="Quan" last="Zhu">Quan Zhu</name>
</country>
</tree>
</affiliations>
</record>

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Serveur d'exploration MERS

Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution.

Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution.

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