Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein.
Identifieur interne : 001B21 ( Main/Exploration ); précédent : 001B20; suivant : 001B22Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein.
Auteurs : Liwei Jiang [République populaire de Chine] ; Nianshuang Wang ; Teng Zuo ; Xuanling Shi ; Kwok-Man Vincent Poon ; Yongkang Wu ; Fei Gao ; Danyang Li ; Ruoke Wang ; Jianying Guo ; Lili Fu ; Kwok-Yung Yuen ; Bo-Jian Zheng ; Xinquan Wang ; Linqi ZhangSource :
- Science translational medicine [ 1946-6242 ] ; 2014.
Descripteurs français
- KwdFr :
- Anticorps antiviraux (immunologie), Anticorps antiviraux (physiologie), Anticorps monoclonaux (immunologie), Anticorps monoclonaux (physiologie), Anticorps neutralisants (immunologie), Anticorps neutralisants (physiologie), Concentration inhibitrice 50, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Humains.
- MESH :
English descriptors
- KwdEn :
- Antibodies, Monoclonal (immunology), Antibodies, Monoclonal (physiology), Antibodies, Neutralizing (immunology), Antibodies, Neutralizing (physiology), Antibodies, Viral (immunology), Antibodies, Viral (physiology), Humans, Inhibitory Concentration 50, Middle East Respiratory Syndrome Coronavirus (immunology).
- MESH :
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral.
- chemical , physiology : Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- Humans, Inhibitory Concentration 50.
Abstract
The recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. Combination of MERS-4 and MERS-27 demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. Biochemical analysis indicated that MERS-4 and MERS-27 blocked RBD interaction with DPP4 on the cell surface. MERS-4, in particular, bound soluble RBD with an about 45-fold higher affinity than DPP4. Mutagenesis analysis suggested that MERS-4 and MERS-27 recognized distinct regions in RBD. These results suggest that MERS-4 and MERS-27 are RBD-specific potent inhibitors and could serve as promising candidates for prophylactic and therapeutic interventions against MERS-CoV infection.
DOI: 10.1126/scitranslmed.3008140
PubMed: 24778414
Affiliations:
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L" first="Liwei" last="Jiang">Liwei Jiang</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Nianshuang" sort="Wang, Nianshuang" uniqKey="Wang N" first="Nianshuang" last="Wang">Nianshuang Wang</name></author><author><name sortKey="Zuo, Teng" sort="Zuo, Teng" uniqKey="Zuo T" first="Teng" last="Zuo">Teng Zuo</name></author><author><name sortKey="Shi, Xuanling" sort="Shi, Xuanling" uniqKey="Shi X" first="Xuanling" last="Shi">Xuanling Shi</name></author><author><name sortKey="Poon, Kwok Man Vincent" sort="Poon, Kwok Man Vincent" uniqKey="Poon K" first="Kwok-Man Vincent" last="Poon">Kwok-Man Vincent Poon</name></author><author><name sortKey="Wu, Yongkang" sort="Wu, Yongkang" uniqKey="Wu Y" first="Yongkang" last="Wu">Yongkang Wu</name></author><author><name sortKey="Gao, Fei" sort="Gao, Fei" uniqKey="Gao F" first="Fei" last="Gao">Fei Gao</name></author><author><name sortKey="Li, Danyang" sort="Li, Danyang" uniqKey="Li D" first="Danyang" last="Li">Danyang Li</name></author><author><name sortKey="Wang, Ruoke" sort="Wang, Ruoke" uniqKey="Wang R" first="Ruoke" last="Wang">Ruoke Wang</name></author><author><name sortKey="Guo, Jianying" sort="Guo, Jianying" uniqKey="Guo J" first="Jianying" last="Guo">Jianying Guo</name></author><author><name sortKey="Fu, Lili" sort="Fu, Lili" uniqKey="Fu L" first="Lili" last="Fu">Lili Fu</name></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></author><author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name></author><author><name sortKey="Wang, Xinquan" sort="Wang, Xinquan" uniqKey="Wang X" first="Xinquan" last="Wang">Xinquan Wang</name></author><author><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name></author></analytic><series><title level="j">Science translational medicine</title><idno type="eISSN">1946-6242</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Monoclonal (immunology)</term><term>Antibodies, Monoclonal (physiology)</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibodies, Neutralizing (physiology)</term><term>Antibodies, Viral (immunology)</term><term>Antibodies, Viral (physiology)</term><term>Humans</term><term>Inhibitory Concentration 50</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Anticorps antiviraux (immunologie)</term><term>Anticorps antiviraux (physiologie)</term><term>Anticorps monoclonaux (immunologie)</term><term>Anticorps monoclonaux (physiologie)</term><term>Anticorps neutralisants (immunologie)</term><term>Anticorps neutralisants (physiologie)</term><term>Concentration inhibitrice 50</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Humains</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</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></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux</term><term>Anticorps neutralisants</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Inhibitory Concentration 50</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Concentration inhibitrice 50</term><term>Humains</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. Combination of MERS-4 and MERS-27 demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. Biochemical analysis indicated that MERS-4 and MERS-27 blocked RBD interaction with DPP4 on the cell surface. MERS-4, in particular, bound soluble RBD with an about 45-fold higher affinity than DPP4. Mutagenesis analysis suggested that MERS-4 and MERS-27 recognized distinct regions in RBD. These results suggest that MERS-4 and MERS-27 are RBD-specific potent inhibitors and could serve as promising candidates for prophylactic and therapeutic interventions against MERS-CoV infection. </div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><noCountry><name sortKey="Fu, Lili" sort="Fu, Lili" uniqKey="Fu L" first="Lili" last="Fu">Lili Fu</name><name sortKey="Gao, Fei" sort="Gao, Fei" uniqKey="Gao F" first="Fei" last="Gao">Fei Gao</name><name sortKey="Guo, Jianying" sort="Guo, Jianying" uniqKey="Guo J" first="Jianying" last="Guo">Jianying Guo</name><name sortKey="Li, Danyang" sort="Li, Danyang" uniqKey="Li D" first="Danyang" last="Li">Danyang Li</name><name sortKey="Poon, Kwok Man Vincent" sort="Poon, Kwok Man Vincent" uniqKey="Poon K" first="Kwok-Man Vincent" last="Poon">Kwok-Man Vincent Poon</name><name sortKey="Shi, Xuanling" sort="Shi, Xuanling" uniqKey="Shi X" first="Xuanling" last="Shi">Xuanling Shi</name><name sortKey="Wang, Nianshuang" sort="Wang, Nianshuang" uniqKey="Wang N" first="Nianshuang" last="Wang">Nianshuang Wang</name><name sortKey="Wang, Ruoke" sort="Wang, Ruoke" uniqKey="Wang R" first="Ruoke" last="Wang">Ruoke Wang</name><name sortKey="Wang, Xinquan" sort="Wang, Xinquan" uniqKey="Wang X" first="Xinquan" last="Wang">Xinquan Wang</name><name sortKey="Wu, Yongkang" sort="Wu, Yongkang" uniqKey="Wu Y" first="Yongkang" last="Wu">Yongkang Wu</name><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name><name sortKey="Zuo, Teng" sort="Zuo, Teng" uniqKey="Zuo T" first="Teng" last="Zuo">Teng Zuo</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Jiang, Liwei" sort="Jiang, Liwei" uniqKey="Jiang L" first="Liwei" last="Jiang">Liwei Jiang</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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