Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets
Identifieur interne : 000847 ( Main/Merge ); précédent : 000846; suivant : 000848Prophylactic 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
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PMC:7113689Le document en format XML
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<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. Thus, mAb administration may be more effective in a prophylactic treatment regimen rather than treatment of MERS.</p>
</div>
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