Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets.
Identifieur interne : 000875 ( PubMed/Corpus ); précédent : 000874; suivant : 000876Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets.
Auteurs : Emmie De Wit ; Friederike Feldmann ; Atsushi Okumura ; Eva Horne ; Elaine Haddock ; Greg Saturday ; Dana Scott ; Karl J. Erlandson ; Neil Stahl ; Leah Lipsich ; Christos A. Kyratsous ; Heinz FeldmannSource :
- Antiviral research [ 1872-9096 ] ; 2018.
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.
DOI: 10.1016/j.antiviral.2018.06.006
PubMed: 29885377
Links to Exploration step
pubmed:29885377Le document en format XML
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Kyratsous</name><affiliation><nlm:affiliation>Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Antiviral research</title><idno type="eISSN">1872-9096</idno><imprint><date when="2018" type="published">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="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</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="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="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></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29885377</PMID><DateCompleted><Year>2019</Year><Month>08</Month><Day>06</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>07</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1872-9096</ISSN><JournalIssue CitedMedium="Internet"><Volume>156</Volume><PubDate><Year>2018</Year><Month>08</Month></PubDate></JournalIssue><Title>Antiviral research</Title><ISOAbbreviation>Antiviral Res.</ISOAbbreviation></Journal><ArticleTitle>Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets.</ArticleTitle><Pagination><MedlinePgn>64-71</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0166-3542(18)30184-0</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.antiviral.2018.06.006</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>Copyright © 2018 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>de Wit</LastName><ForeName>Emmie</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. Electronic address: emmie.dewit@nih.gov.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Feldmann</LastName><ForeName>Friederike</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Okumura</LastName><ForeName>Atsushi</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Horne</LastName><ForeName>Eva</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haddock</LastName><ForeName>Elaine</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saturday</LastName><ForeName>Greg</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scott</LastName><ForeName>Dana</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Erlandson</LastName><ForeName>Karl J</ForeName><Initials>KJ</Initials><AffiliationInfo><Affiliation>Biomedical Advanced Research and Development Authority, Washington, DC, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stahl</LastName><ForeName>Neil</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lipsich</LastName><ForeName>Leah</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kyratsous</LastName><ForeName>Christos A</ForeName><Initials>CA</Initials><AffiliationInfo><Affiliation>Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Feldmann</LastName><ForeName>Heinz</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>06</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Antiviral Res</MedlineTA><NlmUniqueID>8109699</NlmUniqueID><ISSNLinking>0166-3542</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000911">Antibodies, Monoclonal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance></Chemical></ChemicalList><MeshHeadingList><MeshHeading><DescriptorName UI="D061605" MajorTopicYN="N">Administration, Intravenous</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000911" MajorTopicYN="N">Antibodies, Monoclonal</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002144" MajorTopicYN="N">Callithrix</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008168" MajorTopicYN="N">Lung</DescriptorName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019562" MajorTopicYN="N">Viral Load</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Animal 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| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |