Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets
Identifieur interne : 000844 ( Main/Exploration ); précédent : 000843; suivant : 000845Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets
Auteurs : Emmie De Wit [États-Unis] ; Friederike Feldmann [États-Unis] ; Atsushi Okumura [États-Unis] ; Eva Horne [États-Unis] ; Elaine Haddock [États-Unis] ; Greg Saturday [États-Unis] ; Dana Scott [États-Unis] ; Karl J. Erlandson [États-Unis] ; Neil Stahl [États-Unis] ; Leah Lipsich [États-Unis] ; Christos A. Kyratsous [États-Unis] ; Heinz Feldmann [États-Unis]Source :
- Antiviral Research [ 0166-3542 ] ; 2018.
Descripteurs français
- KwdFr :
- Administration par voie intraveineuse, Animaux, Anticorps antiviraux (administration et posologie), Anticorps monoclonaux (administration et posologie), Callithrix, Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification), Infections à coronavirus (), Infections à coronavirus (anatomopathologie), Infections à coronavirus (traitement médicamenteux), Modèles animaux de maladie humaine, Poumon (virologie), Résultat thérapeutique.
- MESH :
- administration et posologie : Anticorps antiviraux, Anticorps monoclonaux.
- anatomopathologie : Infections à coronavirus.
- immunologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- isolement et purification : Coronavirus du syndrome respiratoire du Moyen-Orient.
- traitement médicamenteux : Infections à coronavirus.
- virologie : Poumon.
- Administration par voie intraveineuse, Animaux, Callithrix, Charge virale, Infections à coronavirus, Modèles animaux de maladie humaine, Résultat thérapeutique.
English descriptors
- KwdEn :
- Administration, Intravenous, Animals, Antibodies, Monoclonal (administration & dosage), Antibodies, Viral (administration & dosage), Callithrix, Coronavirus Infections (drug therapy), Coronavirus Infections (pathology), Coronavirus Infections (prevention & control), Disease Models, Animal, Lung (virology), Middle East Respiratory Syndrome Coronavirus (immunology), Middle East Respiratory Syndrome Coronavirus (isolation & purification), Treatment Outcome, Viral Load.
- MESH :
- chemical , administration & dosage : Antibodies, Monoclonal, Antibodies, Viral.
- drug therapy : Coronavirus Infections.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- isolation & purification : Middle East Respiratory Syndrome Coronavirus.
- pathology : Coronavirus Infections.
- prevention & control : Coronavirus Infections.
- virology : Lung.
- Administration, Intravenous, Animals, Callithrix, Disease Models, Animal, Treatment Outcome, Viral Load.
Abstract
The high case-fatality rate of confirmed MERS-CoV infections underlines the urgent need for an effective treatment to reduce the disease severity and mortality. REGN3051 and REGN3048 are two fully human neutralizing monoclonal antibodies (mAb) against MERS-CoV that reduced virus replication in mice expressing human DPP4 upon prophylactic and therapeutic treatment. Here, we evaluated the prophylactic and therapeutic efficacy of REGN3048 and REGN3051 in the common marmoset model of MERS-CoV infection. Intravenous administration of mAb resulted in high levels of MERS-CoV-neutralizing activity in circulating blood. When animals were treated with mAbs one day before challenge, respiratory disease was less severe and, in animals treated with both REGN3048 and REGN3051, viral loads in the lungs were reduced. However, therapeutic treatment on day one after challenge was less efficacious as it did not prevent the development of severe respiratory disease and all treated animals developed bronchointerstitial pneumonia of similar severity as the control animals. Thus, mAb administration may be more effective in a prophylactic treatment regimen rather than treatment of MERS.
Url:
DOI: 10.1016/j.antiviral.2018.06.006
PubMed: 29885377
PubMed Central: 7113689
Affiliations:
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MT</wicri:regionArea><placeName><region type="state">Montana</region></placeName></affiliation></author><author><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name><affiliation wicri:level="4"><nlm:aff id="aff3">Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region><settlement type="city">New York</settlement></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Horne, Eva" sort="Horne, Eva" uniqKey="Horne E" first="Eva" last="Horne">Eva Horne</name><affiliation wicri:level="2"><nlm:aff id="aff1">Laboratory of Virology, National Institute of Allergy and 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Greg" sort="Saturday, Greg" uniqKey="Saturday G" first="Greg" last="Saturday">Greg Saturday</name><affiliation wicri:level="2"><nlm:aff id="aff2">Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT</wicri:regionArea><placeName><region type="state">Montana</region></placeName></affiliation></author><author><name sortKey="Scott, Dana" sort="Scott, Dana" uniqKey="Scott D" first="Dana" last="Scott">Dana Scott</name><affiliation wicri:level="2"><nlm:aff id="aff2">Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT</wicri:regionArea><placeName><region type="state">Montana</region></placeName></affiliation></author><author><name sortKey="Erlandson, Karl J" sort="Erlandson, Karl J" uniqKey="Erlandson K" first="Karl J." last="Erlandson">Karl J. Erlandson</name><affiliation wicri:level="2"><nlm:aff id="aff4">Biomedical Advanced Research and Development Authority, Washington, DC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biomedical Advanced Research and Development Authority, Washington, DC</wicri:regionArea><placeName><region type="state">District de Columbia</region></placeName></affiliation></author><author><name sortKey="Stahl, Neil" sort="Stahl, Neil" uniqKey="Stahl N" first="Neil" last="Stahl">Neil Stahl</name><affiliation wicri:level="2"><nlm:aff id="aff5">Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Regeneron Pharmaceuticals, Inc., Tarrytown, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Lipsich, Leah" sort="Lipsich, Leah" uniqKey="Lipsich L" first="Leah" last="Lipsich">Leah Lipsich</name><affiliation wicri:level="2"><nlm:aff id="aff5">Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Regeneron Pharmaceuticals, Inc., Tarrytown, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Kyratsous, Christos A" sort="Kyratsous, Christos A" uniqKey="Kyratsous C" first="Christos A." last="Kyratsous">Christos A. Kyratsous</name><affiliation wicri:level="2"><nlm:aff id="aff5">Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Regeneron Pharmaceuticals, Inc., Tarrytown, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation wicri:level="2"><nlm:aff id="aff1">Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT</wicri:regionArea><placeName><region type="state">Montana</region></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="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Intravenous</term><term>Animals</term><term>Antibodies, Monoclonal (administration & dosage)</term><term>Antibodies, Viral (administration & dosage)</term><term>Callithrix</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (pathology)</term><term>Coronavirus Infections (prevention & control)</term><term>Disease Models, Animal</term><term>Lung (virology)</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Middle East Respiratory Syndrome Coronavirus (isolation & purification)</term><term>Treatment Outcome</term><term>Viral Load</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Administration par voie intraveineuse</term><term>Animaux</term><term>Anticorps antiviraux (administration et posologie)</term><term>Anticorps monoclonaux (administration et posologie)</term><term>Callithrix</term><term>Charge virale</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification)</term><term>Infections à coronavirus ()</term><term>Infections à coronavirus (anatomopathologie)</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Modèles animaux de maladie humaine</term><term>Poumon (virologie)</term><term>Résultat thérapeutique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à 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>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="isolation & purification" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</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>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Intravenous</term><term>Animals</term><term>Callithrix</term><term>Disease Models, Animal</term><term>Treatment Outcome</term><term>Viral Load</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Administration par voie intraveineuse</term><term>Animaux</term><term>Callithrix</term><term>Charge virale</term><term>Infections à coronavirus</term><term>Modèles animaux de maladie humaine</term><term>Résultat thérapeutique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The high case-fatality rate of confirmed MERS-CoV infections underlines the urgent need for an effective treatment to reduce the disease severity and mortality. REGN3051 and REGN3048 are two fully human neutralizing monoclonal antibodies (mAb) against MERS-CoV that reduced virus replication in mice expressing human DPP4 upon prophylactic and therapeutic treatment. Here, we evaluated the prophylactic and therapeutic efficacy of REGN3048 and REGN3051 in the common marmoset model of MERS-CoV infection. Intravenous administration of mAb resulted in high levels of MERS-CoV-neutralizing activity in circulating blood. When animals were treated with mAbs one day before challenge, respiratory disease was less severe and, in animals treated with both REGN3048 and REGN3051, viral loads in the lungs were reduced. However, therapeutic treatment on day one after challenge was less efficacious as it did not prevent the development of severe respiratory disease and all treated animals developed bronchointerstitial pneumonia of similar severity as the control animals. 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Xia</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>District de Columbia</li><li>Montana</li><li>État de New York</li></region><settlement><li>New York</li></settlement><orgName><li>Université Columbia</li></orgName></list><tree><country name="États-Unis"><region name="Montana"><name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</name></region><name sortKey="Erlandson, Karl J" sort="Erlandson, Karl J" uniqKey="Erlandson K" first="Karl J." last="Erlandson">Karl J. Erlandson</name><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><name sortKey="Haddock, Elaine" sort="Haddock, Elaine" uniqKey="Haddock E" first="Elaine" last="Haddock">Elaine Haddock</name><name sortKey="Horne, Eva" sort="Horne, Eva" uniqKey="Horne E" first="Eva" last="Horne">Eva Horne</name><name sortKey="Kyratsous, Christos A" sort="Kyratsous, Christos A" uniqKey="Kyratsous C" first="Christos A." last="Kyratsous">Christos A. Kyratsous</name><name sortKey="Lipsich, Leah" sort="Lipsich, Leah" uniqKey="Lipsich L" first="Leah" last="Lipsich">Leah Lipsich</name><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name><name sortKey="Saturday, Greg" sort="Saturday, Greg" uniqKey="Saturday G" first="Greg" last="Saturday">Greg Saturday</name><name sortKey="Scott, Dana" sort="Scott, Dana" uniqKey="Scott D" first="Dana" last="Scott">Dana Scott</name><name sortKey="Stahl, Neil" sort="Stahl, Neil" uniqKey="Stahl N" first="Neil" last="Stahl">Neil Stahl</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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