Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection
Identifieur interne : 001019 ( Main/Exploration ); précédent : 001018; suivant : 001020Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection
Auteurs : Hongjie Qiu [République populaire de Chine] ; Shihui Sun [République populaire de Chine] ; He Xiao [République populaire de Chine] ; Jiannan Feng [République populaire de Chine] ; Yan Guo [République populaire de Chine] ; Wanbo Tai [République populaire de Chine, États-Unis] ; Yufei Wang [République populaire de Chine, États-Unis] ; Lanying Du [États-Unis] ; Guangyu Zhao [République populaire de Chine] ; Yusen Zhou [République populaire de Chine]Source :
- Antiviral Research [ 0166-3542 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (administration et posologie), Anticorps antiviraux (immunologie), Anticorps monoclonaux humanisés (administration et posologie), Anticorps monoclonaux humanisés (immunologie), Anticorps neutralisants (administration et posologie), Anticorps neutralisants (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Dipeptidyl peptidase 4 (métabolisme), Femelle, Humains, Infections à coronavirus (immunologie), Infections à coronavirus (mortalité), Infections à coronavirus (traitement médicamenteux), Infections à coronavirus (virologie), Liaison aux protéines, Lignée cellulaire, Modèles animaux de maladie humaine, Réactions croisées (immunologie), Récepteurs viraux (métabolisme), Souris, Souris transgéniques, Tests de neutralisation, Épitopes (immunologie).
- MESH :
- administration et posologie : Anticorps antiviraux, Anticorps monoclonaux humanisés, Anticorps neutralisants.
- immunologie : Anticorps antiviraux, Anticorps monoclonaux humanisés, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Infections à coronavirus, Réactions croisées, Épitopes.
- mortalité : Infections à coronavirus.
- métabolisme : Dipeptidyl peptidase 4, Récepteurs viraux.
- traitement médicamenteux : Infections à coronavirus.
- virologie : Infections à coronavirus.
- Animaux, Coronavirus du syndrome respiratoire du Moyen-Orient, Femelle, Humains, Liaison aux protéines, Lignée cellulaire, Modèles animaux de maladie humaine, Souris, Souris transgéniques, Tests de neutralisation.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal, Humanized (administration & dosage), Antibodies, Monoclonal, Humanized (immunology), Antibodies, Neutralizing (administration & dosage), Antibodies, Neutralizing (immunology), Antibodies, Viral (administration & dosage), Antibodies, Viral (immunology), Cell Line, Coronavirus Infections (drug therapy), Coronavirus Infections (immunology), Coronavirus Infections (mortality), Coronavirus Infections (virology), Cross Reactions (immunology), Dipeptidyl Peptidase 4 (metabolism), Disease Models, Animal, Epitopes (immunology), Female, Humans, Mice, Mice, Transgenic, Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (immunology), Neutralization Tests, Protein Binding, Receptors, Virus (metabolism).
- MESH :
- chemical , administration & dosage : Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing, Antibodies, Viral.
- chemical , immunology : Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing, Antibodies, Viral, Epitopes.
- drug effects : Middle East Respiratory Syndrome Coronavirus.
- drug therapy : Coronavirus Infections.
- immunology : Coronavirus Infections, Cross Reactions, Middle East Respiratory Syndrome Coronavirus.
- chemical , metabolism : Dipeptidyl Peptidase 4, Receptors, Virus.
- mortality : Coronavirus Infections.
- virology : Coronavirus Infections.
- Animals, Cell Line, Disease Models, Animal, Female, Humans, Mice, Mice, Transgenic, Neutralization Tests, Protein Binding.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases.
Url:
DOI: 10.1016/j.antiviral.2016.06.003
PubMed: 27312105
PubMed Central: 5109928
Affiliations:
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sortKey="Feng, Jiannan" sort="Feng, Jiannan" uniqKey="Feng J" first="Jiannan" last="Feng">Jiannan Feng</name><affiliation wicri:level="3"><nlm:aff id="aff2">Beijing Institute of Basic Medical Sciences, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing Institute of Basic Medical Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Guo, Yan" sort="Guo, Yan" uniqKey="Guo Y" first="Yan" last="Guo">Yan Guo</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Tai, Wanbo" sort="Tai, Wanbo" uniqKey="Tai W" first="Wanbo" last="Tai">Wanbo Tai</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3">Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Wang, Yufei" sort="Wang, Yufei" uniqKey="Wang Y" first="Yufei" last="Wang">Yufei Wang</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3">Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name><affiliation wicri:level="2"><nlm:aff id="aff3">Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author></analytic><series><title level="j">Antiviral Research</title><idno type="ISSN">0166-3542</idno><idno type="eISSN">1872-9096</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Monoclonal, Humanized (administration & dosage)</term><term>Antibodies, Monoclonal, Humanized (immunology)</term><term>Antibodies, Neutralizing (administration & dosage)</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibodies, Viral (administration & dosage)</term><term>Antibodies, Viral (immunology)</term><term>Cell Line</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (mortality)</term><term>Coronavirus Infections (virology)</term><term>Cross Reactions (immunology)</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Disease Models, Animal</term><term>Epitopes (immunology)</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Neutralization Tests</term><term>Protein Binding</term><term>Receptors, Virus (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (administration et posologie)</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps monoclonaux humanisés (administration et posologie)</term><term>Anticorps monoclonaux humanisés (immunologie)</term><term>Anticorps neutralisants (administration et posologie)</term><term>Anticorps neutralisants (immunologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Dipeptidyl peptidase 4 (métabolisme)</term><term>Femelle</term><term>Humains</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (mortalité)</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Infections à coronavirus (virologie)</term><term>Liaison aux protéines</term><term>Lignée cellulaire</term><term>Modèles animaux de maladie humaine</term><term>Réactions croisées (immunologie)</term><term>Récepteurs viraux (métabolisme)</term><term>Souris</term><term>Souris transgéniques</term><term>Tests de neutralisation</term><term>Épitopes (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Epitopes</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux humanisés</term><term>Anticorps neutralisants</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux humanisés</term><term>Anticorps neutralisants</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Infections à coronavirus</term><term>Réactions croisées</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term><term>Cross Reactions</term><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>Receptors, Virus</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Dipeptidyl peptidase 4</term><term>Récepteurs viraux</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</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>Cell Line</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>Neutralization Tests</term><term>Protein Binding</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Femelle</term><term>Humains</term><term>Liaison aux protéines</term><term>Lignée cellulaire</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Souris transgéniques</term><term>Tests de neutralisation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bonavia, A" uniqKey="Bonavia A">A. 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