A novel neutralizing monoclonal antibody targeting the N-terminal domain of the MERS-CoV spike protein
Identifieur interne : 000F10 ( Main/Exploration ); précédent : 000F09; suivant : 000F11A novel neutralizing monoclonal antibody targeting the N-terminal domain of the MERS-CoV spike protein
Auteurs : Yingzhu Chen [République populaire de Chine] ; Shuai Lu [République populaire de Chine] ; Hao Jia [République populaire de Chine] ; Yao Deng [République populaire de Chine] ; Jianfang Zhou [République populaire de Chine] ; Baoying Huang [République populaire de Chine] ; Yueyang Yu [République populaire de Chine] ; Jiaming Lan [République populaire de Chine] ; Wenling Wang [République populaire de Chine] ; Yongliang Lou [République populaire de Chine] ; Kun Qin [République populaire de Chine] ; Wenjie Tan [République populaire de Chine]Source :
- Emerging Microbes & Infections [ 2222-1751 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps monoclonaux (immunologie), Anticorps neutralisants (immunologie), Cellules Vero, Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Glycoprotéine de spicule des coronavirus (), Glycoprotéine de spicule des coronavirus (administration et posologie), Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (immunologie), Humains, Immunisation, Infections à coronavirus (), Liaison aux protéines, Modèles moléculaires, Récepteurs viraux, Souris, Vaccins antiviraux.
- MESH :
- administration et posologie : Glycoprotéine de spicule des coronavirus.
- génétique : Glycoprotéine de spicule des coronavirus.
- immunologie : Anticorps antiviraux, Anticorps monoclonaux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus.
- Animaux, Cellules Vero, Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Humains, Immunisation, Infections à coronavirus, Liaison aux protéines, Modèles moléculaires, Récepteurs viraux, Souris, Vaccins antiviraux.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (immunology), Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Chlorocebus aethiops, Coronavirus Infections (therapy), Humans, Immunization, Mice, Middle East Respiratory Syndrome Coronavirus (chemistry), Middle East Respiratory Syndrome Coronavirus (immunology), Models, Molecular, Protein Binding, Receptors, Virus, Spike Glycoprotein, Coronavirus (administration & dosage), Spike Glycoprotein, Coronavirus (chemistry), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology), Vero Cells, Viral Vaccines.
- MESH :
- chemical , administration & dosage : Spike Glycoprotein, Coronavirus.
- chemical , chemistry : Spike Glycoprotein, Coronavirus.
- chemical , genetics : Spike Glycoprotein, Coronavirus.
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Spike Glycoprotein, Coronavirus.
- chemistry : Middle East Respiratory Syndrome Coronavirus.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- therapy : Coronavirus Infections.
- Animals, Chlorocebus aethiops, Humans, Immunization, Mice, Models, Molecular, Protein Binding, Receptors, Virus, Vero Cells, Viral Vaccines.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused fatal infections, some through hospital-acquired transmission, in affected regions since its emergence in 2012. Although the virus is not pandemic among humans, it poses a great threat to public health due to its zoonotic origin. Thus, both preventative and therapeutic countermeasures are urgently needed. In this study, we discovered a panel of neutralizing monoclonal antibodies (mAbs) against MERS-CoV, which mapped to a wide range of regions on the spike (S) protein of the virus. In addition to mAbs with neutralizing epitopes located on the receptor-binding domain, one mAb, 5F9, which binds to the N-terminal domain (NTD) of the MERS-CoV S1 subunit, showed efficient neutralizing activity against the wild-type MERS-CoV strain EMC/2012, with a half maximal inhibitory concentration of 0.2 μg/mL. We concluded that a novel neutralizing epitope for MERS-CoV also resides on the NTD of the S protein, indicating that the NTD might be important during the viral infection process. Our findings have significant implications for further vaccine design and for the development of prophylactic and therapeutic monoclonal immunotherapies against MERS-CoV infection.
Url:
DOI: 10.1038/emi.2017.18
PubMed: 28536429
PubMed Central: 5520482
Affiliations:
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Le document en format XML
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sort="Lu, Shuai" uniqKey="Lu S" first="Shuai" last="Lu">Shuai Lu</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC</institution>, Beijing 102206,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jia, Hao" sort="Jia, Hao" uniqKey="Jia H" first="Hao" last="Jia">Hao Jia</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>School of Laboratory Medicine and Life Science, Institute of Medical VirologyWenzhou Medical University</institution>, Wenzhou 325035,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC</institution>, Beijing 102206,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Deng, Yao" sort="Deng, Yao" uniqKey="Deng Y" first="Yao" last="Deng">Yao Deng</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC</institution>, Beijing 102206,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Jianfang" sort="Zhou, Jianfang" uniqKey="Zhou J" first="Jianfang" last="Zhou">Jianfang Zhou</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC</institution>, Beijing 102206,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Huang, Baoying" sort="Huang, Baoying" uniqKey="Huang B" first="Baoying" last="Huang">Baoying Huang</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC</institution>, Beijing 102206,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yu, Yueyang" sort="Yu, Yueyang" uniqKey="Yu Y" first="Yueyang" last="Yu">Yueyang Yu</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC</institution>, Beijing 102206,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lan, Jiaming" sort="Lan, Jiaming" uniqKey="Lan J" first="Jiaming" last="Lan">Jiaming Lan</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC</institution>, Beijing 102206,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Wenling" sort="Wang, Wenling" uniqKey="Wang W" first="Wenling" last="Wang">Wenling Wang</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC</institution>, Beijing 102206,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lou, Yongliang" sort="Lou, Yongliang" uniqKey="Lou Y" first="Yongliang" last="Lou">Yongliang Lou</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>School of Laboratory Medicine and Life Science, Institute of Medical VirologyWenzhou Medical University</institution>, Wenzhou 325035,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Qin, Kun" sort="Qin, Kun" uniqKey="Qin K" first="Kun" last="Qin">Kun Qin</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC</institution>, Beijing 102206,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>School of Laboratory Medicine and Life Science, Institute of Medical VirologyWenzhou Medical University</institution>, Wenzhou 325035,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC</institution>, Beijing 102206,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</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="2017">2017</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>Chlorocebus aethiops</term><term>Coronavirus Infections (therapy)</term><term>Humans</term><term>Immunization</term><term>Mice</term><term>Middle East Respiratory Syndrome Coronavirus (chemistry)</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Models, Molecular</term><term>Protein Binding</term><term>Receptors, Virus</term><term>Spike Glycoprotein, Coronavirus (administration & dosage)</term><term>Spike Glycoprotein, Coronavirus (chemistry)</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Spike Glycoprotein, Coronavirus (immunology)</term><term>Vero Cells</term><term>Viral Vaccines</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>Cellules Vero</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Glycoprotéine de spicule des coronavirus ()</term><term>Glycoprotéine de spicule des coronavirus (administration et posologie)</term><term>Glycoprotéine de spicule des coronavirus (génétique)</term><term>Glycoprotéine de spicule des coronavirus (immunologie)</term><term>Humains</term><term>Immunisation</term><term>Infections à coronavirus ()</term><term>Liaison aux protéines</term><term>Modèles moléculaires</term><term>Récepteurs viraux</term><term>Souris</term><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><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>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</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></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Humans</term><term>Immunization</term><term>Mice</term><term>Models, Molecular</term><term>Protein Binding</term><term>Receptors, Virus</term><term>Vero Cells</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Immunisation</term><term>Infections à coronavirus</term><term>Liaison aux protéines</term><term>Modèles moléculaires</term><term>Récepteurs viraux</term><term>Souris</term><term>Vaccins antiviraux</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) has caused fatal infections, some
through hospital-acquired transmission, in affected regions since its emergence in 2012.
Although the virus is not pandemic among humans, it poses a great threat to public health
due to its zoonotic origin. Thus, both preventative and therapeutic countermeasures are
urgently needed. In this study, we discovered a panel of neutralizing monoclonal
antibodies (mAbs) against MERS-CoV, which mapped to a wide range of regions on the spike
(S) protein of the virus. In addition to mAbs with neutralizing epitopes located on the
receptor-binding domain, one mAb, 5F9, which binds to the N-terminal domain (NTD) of the
MERS-CoV S1 subunit, showed efficient neutralizing activity against the wild-type MERS-CoV
strain EMC/2012, with a half maximal inhibitory concentration of 0.2 μg/mL. We concluded
that a novel neutralizing epitope for MERS-CoV also resides on the NTD of the S protein,
indicating that the NTD might be important during the viral infection process. Our
findings have significant implications for further vaccine design and for the development
of prophylactic and therapeutic monoclonal immunotherapies against MERS-CoV infection.</p><p><italic>Emerging Microbes & Infections</italic> (2017) <bold>6,</bold> e37;
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de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Chen, Yingzhu" sort="Chen, Yingzhu" uniqKey="Chen Y" first="Yingzhu" last="Chen">Yingzhu Chen</name></noRegion><name sortKey="Chen, Yingzhu" sort="Chen, Yingzhu" uniqKey="Chen Y" first="Yingzhu" last="Chen">Yingzhu Chen</name><name sortKey="Deng, Yao" sort="Deng, Yao" uniqKey="Deng Y" first="Yao" last="Deng">Yao Deng</name><name sortKey="Huang, Baoying" sort="Huang, Baoying" uniqKey="Huang B" first="Baoying" last="Huang">Baoying Huang</name><name sortKey="Jia, Hao" sort="Jia, Hao" uniqKey="Jia H" first="Hao" last="Jia">Hao Jia</name><name sortKey="Jia, Hao" sort="Jia, Hao" uniqKey="Jia H" first="Hao" last="Jia">Hao Jia</name><name sortKey="Lan, Jiaming" sort="Lan, Jiaming" uniqKey="Lan J" first="Jiaming" last="Lan">Jiaming Lan</name><name sortKey="Lou, Yongliang" sort="Lou, Yongliang" uniqKey="Lou Y" first="Yongliang" last="Lou">Yongliang Lou</name><name sortKey="Lu, Shuai" sort="Lu, Shuai" uniqKey="Lu S" first="Shuai" last="Lu">Shuai Lu</name><name sortKey="Qin, Kun" sort="Qin, Kun" uniqKey="Qin K" first="Kun" last="Qin">Kun Qin</name><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><name sortKey="Wang, Wenling" sort="Wang, Wenling" uniqKey="Wang W" first="Wenling" last="Wang">Wenling Wang</name><name sortKey="Yu, Yueyang" sort="Yu, Yueyang" uniqKey="Yu Y" first="Yueyang" last="Yu">Yueyang Yu</name><name sortKey="Zhou, Jianfang" sort="Zhou, Jianfang" uniqKey="Zhou J" first="Jianfang" last="Zhou">Jianfang Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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