Intranasal antibody gene transfer in mice and ferrets elicits broad protection against pandemic influenza.
Identifieur interne : 000978 ( PubMed/Checkpoint ); précédent : 000977; suivant : 000979Intranasal antibody gene transfer in mice and ferrets elicits broad protection against pandemic influenza.
Auteurs : Maria P. Limberis [États-Unis] ; Virginie S. Adam ; Gary Wong ; Jason Gren ; Darwyn Kobasa ; Ted M. Ross ; Gary P. Kobinger ; Anna Tretiakova ; James M. WilsonSource :
- Science translational medicine [ 1946-6242 ] ; 2013.
Descripteurs français
- KwdFr :
- Administration par voie nasale, Animaux, Anticorps antiviraux (administration et posologie), Anticorps antiviraux (génétique), Anticorps neutralisants (administration et posologie), Anticorps neutralisants (génétique), Dependovirus (génétique), Femelle, Furets, Infections à Orthomyxoviridae (), Macaca mulatta, Relation dose-réponse (immunologie), Souris, Souris de lignée BALB C, Techniques de transfert de gènes.
- MESH :
- administration et posologie : Anticorps antiviraux, Anticorps neutralisants.
- génétique : Anticorps antiviraux, Anticorps neutralisants, Dependovirus.
- Administration par voie nasale, Animaux, Femelle, Furets, Infections à Orthomyxoviridae, Macaca mulatta, Relation dose-réponse (immunologie), Souris, Souris de lignée BALB C, Techniques de transfert de gènes.
English descriptors
- KwdEn :
- Administration, Intranasal, Animals, Antibodies, Neutralizing (administration & dosage), Antibodies, Neutralizing (genetics), Antibodies, Viral (administration & dosage), Antibodies, Viral (genetics), Dependovirus (genetics), Dose-Response Relationship, Immunologic, Female, Ferrets, Gene Transfer Techniques, Macaca mulatta, Mice, Mice, Inbred BALB C, Orthomyxoviridae Infections (prevention & control).
- MESH :
- chemical , administration & dosage : Antibodies, Neutralizing, Antibodies, Viral.
- chemical , genetics : Antibodies, Neutralizing, Antibodies, Viral.
- genetics : Dependovirus.
- prevention & control : Orthomyxoviridae Infections.
- Administration, Intranasal, Animals, Dose-Response Relationship, Immunologic, Female, Ferrets, Gene Transfer Techniques, Macaca mulatta, Mice, Mice, Inbred BALB C.
Abstract
The emergence of a new influenza pandemic remains a threat that could result in a substantial loss of life and economic disruption worldwide. Advances in human antibody isolation have led to the discovery of monoclonal antibodies (mAbs) that have broad neutralizing activity against various influenza strains, although their direct use for prophylaxis is impractical. To overcome this limitation, our approach is to deliver antibody via adeno-associated virus (AAV) vectors to the site of initial infection, which, for respiratory viruses such as influenza, is the nasopharyngeal mucosa. AAV vectors based on serotype 9 were engineered to express a modified version of the previously isolated broadly neutralizing mAb to influenza A, FI6. We demonstrate that intranasal delivery of AAV9.FI6 into mice afforded complete protection and log reductions in viral load to 100 LD₅₀ (median lethal dose) of three clinical isolates of H5N1 and two clinical isolates of H1N1, all of which have been associated with historic human pandemics (including H1N1 1918). Similarly, complete protection was achieved in ferrets challenged with lethal doses of H5N1 and H1N1. This approach serves as a platform for the prevention of natural or deliberate respiratory diseases for which a protective antibody is available.
DOI: 10.1126/scitranslmed.3006299
PubMed: 23720583
Affiliations:
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Adam</name></author><author><name sortKey="Wong, Gary" sort="Wong, Gary" uniqKey="Wong G" first="Gary" last="Wong">Gary Wong</name></author><author><name sortKey="Gren, Jason" sort="Gren, Jason" uniqKey="Gren J" first="Jason" last="Gren">Jason Gren</name></author><author><name sortKey="Kobasa, Darwyn" sort="Kobasa, Darwyn" uniqKey="Kobasa D" first="Darwyn" last="Kobasa">Darwyn Kobasa</name></author><author><name sortKey="Ross, Ted M" sort="Ross, Ted M" uniqKey="Ross T" first="Ted M" last="Ross">Ted M. Ross</name></author><author><name sortKey="Kobinger, Gary P" sort="Kobinger, Gary P" uniqKey="Kobinger G" first="Gary P" last="Kobinger">Gary P. Kobinger</name></author><author><name sortKey="Tretiakova, Anna" sort="Tretiakova, Anna" uniqKey="Tretiakova A" first="Anna" last="Tretiakova">Anna Tretiakova</name></author><author><name sortKey="Wilson, James M" sort="Wilson, James M" uniqKey="Wilson J" first="James M" last="Wilson">James M. Wilson</name></author></analytic><series><title level="j">Science translational medicine</title><idno type="eISSN">1946-6242</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Intranasal</term><term>Animals</term><term>Antibodies, Neutralizing (administration & dosage)</term><term>Antibodies, Neutralizing (genetics)</term><term>Antibodies, Viral (administration & dosage)</term><term>Antibodies, Viral (genetics)</term><term>Dependovirus (genetics)</term><term>Dose-Response Relationship, Immunologic</term><term>Female</term><term>Ferrets</term><term>Gene Transfer Techniques</term><term>Macaca mulatta</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Orthomyxoviridae Infections (prevention & control)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Administration par voie nasale</term><term>Animaux</term><term>Anticorps antiviraux (administration et posologie)</term><term>Anticorps antiviraux (génétique)</term><term>Anticorps neutralisants (administration et posologie)</term><term>Anticorps neutralisants (génétique)</term><term>Dependovirus (génétique)</term><term>Femelle</term><term>Furets</term><term>Infections à Orthomyxoviridae ()</term><term>Macaca mulatta</term><term>Relation dose-réponse (immunologie)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Techniques de transfert de gènes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Dependovirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Dependovirus</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Intranasal</term><term>Animals</term><term>Dose-Response Relationship, Immunologic</term><term>Female</term><term>Ferrets</term><term>Gene Transfer Techniques</term><term>Macaca mulatta</term><term>Mice</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Administration par voie nasale</term><term>Animaux</term><term>Femelle</term><term>Furets</term><term>Infections à Orthomyxoviridae</term><term>Macaca mulatta</term><term>Relation dose-réponse (immunologie)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Techniques de transfert de gènes</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The emergence of a new influenza pandemic remains a threat that could result in a substantial loss of life and economic disruption worldwide. Advances in human antibody isolation have led to the discovery of monoclonal antibodies (mAbs) that have broad neutralizing activity against various influenza strains, although their direct use for prophylaxis is impractical. To overcome this limitation, our approach is to deliver antibody via adeno-associated virus (AAV) vectors to the site of initial infection, which, for respiratory viruses such as influenza, is the nasopharyngeal mucosa. AAV vectors based on serotype 9 were engineered to express a modified version of the previously isolated broadly neutralizing mAb to influenza A, FI6. We demonstrate that intranasal delivery of AAV9.FI6 into mice afforded complete protection and log reductions in viral load to 100 LD₅₀ (median lethal dose) of three clinical isolates of H5N1 and two clinical isolates of H1N1, all of which have been associated with historic human pandemics (including H1N1 1918). Similarly, complete protection was achieved in ferrets challenged with lethal doses of H5N1 and H1N1. This approach serves as a platform for the prevention of natural or deliberate respiratory diseases for which a protective antibody is available.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23720583</PMID><DateCompleted><Year>2013</Year><Month>12</Month><Day>27</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1946-6242</ISSN><JournalIssue CitedMedium="Internet"><Volume>5</Volume><Issue>187</Issue><PubDate><Year>2013</Year><Month>May</Month><Day>29</Day></PubDate></JournalIssue><Title>Science translational medicine</Title><ISOAbbreviation>Sci Transl Med</ISOAbbreviation></Journal><ArticleTitle>Intranasal antibody gene transfer in mice and ferrets elicits broad protection against pandemic influenza.</ArticleTitle><Pagination><MedlinePgn>187ra72</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1126/scitranslmed.3006299</ELocationID><Abstract><AbstractText>The emergence of a new influenza pandemic remains a threat that could result in a substantial loss of life and economic disruption worldwide. Advances in human antibody isolation have led to the discovery of monoclonal antibodies (mAbs) that have broad neutralizing activity against various influenza strains, although their direct use for prophylaxis is impractical. To overcome this limitation, our approach is to deliver antibody via adeno-associated virus (AAV) vectors to the site of initial infection, which, for respiratory viruses such as influenza, is the nasopharyngeal mucosa. AAV vectors based on serotype 9 were engineered to express a modified version of the previously isolated broadly neutralizing mAb to influenza A, FI6. We demonstrate that intranasal delivery of AAV9.FI6 into mice afforded complete protection and log reductions in viral load to 100 LD₅₀ (median lethal dose) of three clinical isolates of H5N1 and two clinical isolates of H1N1, all of which have been associated with historic human pandemics (including H1N1 1918). Similarly, complete protection was achieved in ferrets challenged with lethal doses of H5N1 and H1N1. This approach serves as a platform for the prevention of natural or deliberate respiratory diseases for which a protective antibody is available.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Limberis</LastName><ForeName>Maria P</ForeName><Initials>MP</Initials><AffiliationInfo><Affiliation>Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104, USA. limberis@mail.med.upenn.edu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Adam</LastName><ForeName>Virginie S</ForeName><Initials>VS</Initials></Author><Author ValidYN="Y"><LastName>Wong</LastName><ForeName>Gary</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Gren</LastName><ForeName>Jason</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Kobasa</LastName><ForeName>Darwyn</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Ross</LastName><ForeName>Ted M</ForeName><Initials>TM</Initials></Author><Author ValidYN="Y"><LastName>Kobinger</LastName><ForeName>Gary P</ForeName><Initials>GP</Initials></Author><Author ValidYN="Y"><LastName>Tretiakova</LastName><ForeName>Anna</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Wilson</LastName><ForeName>James M</ForeName><Initials>JM</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 GM083602</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>246355</GrantID><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant><Grant><GrantID>GM083602</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType 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UI="D008253" MajorTopicYN="N">Macaca mulatta</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009976" MajorTopicYN="N">Orthomyxoviridae Infections</DescriptorName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>5</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>5</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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first="Virginie S" last="Adam">Virginie S. Adam</name><name sortKey="Gren, Jason" sort="Gren, Jason" uniqKey="Gren J" first="Jason" last="Gren">Jason Gren</name><name sortKey="Kobasa, Darwyn" sort="Kobasa, Darwyn" uniqKey="Kobasa D" first="Darwyn" last="Kobasa">Darwyn Kobasa</name><name sortKey="Kobinger, Gary P" sort="Kobinger, Gary P" uniqKey="Kobinger G" first="Gary P" last="Kobinger">Gary P. Kobinger</name><name sortKey="Ross, Ted M" sort="Ross, Ted M" uniqKey="Ross T" first="Ted M" last="Ross">Ted M. Ross</name><name sortKey="Tretiakova, Anna" sort="Tretiakova, Anna" uniqKey="Tretiakova A" first="Anna" last="Tretiakova">Anna Tretiakova</name><name sortKey="Wilson, James M" sort="Wilson, James M" uniqKey="Wilson J" first="James M" last="Wilson">James M. Wilson</name><name sortKey="Wong, Gary" sort="Wong, Gary" uniqKey="Wong G" first="Gary" last="Wong">Gary Wong</name></noCountry><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Limberis, Maria P" sort="Limberis, Maria P" uniqKey="Limberis M" first="Maria P" last="Limberis">Maria P. Limberis</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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