Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza
Identifieur interne : 001660 ( Ncbi/Checkpoint ); précédent : 001659; suivant : 001661Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza
Auteurs : Maria P. Limberis [États-Unis] ; Virginie S. Adam [États-Unis] ; Gary Wong [Canada] ; Jason Gren [Canada] ; Darwyn Kobasa [Canada] ; Ted M. Ross [États-Unis] ; Gary P. Kobinger [Canada] ; Anna Tretiakova [États-Unis] ; James M. Wilson [États-Unis]Source :
- Science translational medicine [ 1946-6234 ] ; 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.
Url:
DOI: 10.1126/scitranslmed.3006299
PubMed: 23720583
PubMed Central: 4596530
Affiliations:
- Canada, États-Unis
- Manitoba, Pennsylvanie
- Pittsburgh, Winnipeg
- Université de Pittsburgh, Université du Manitoba
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PMC:4596530Le document en format XML
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Limberis</name><affiliation wicri:level="2"><nlm:aff id="A1">Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Adam, Virginie S" sort="Adam, Virginie S" uniqKey="Adam V" first="Virginie S." last="Adam">Virginie S. Adam</name><affiliation wicri:level="2"><nlm:aff id="A1">Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Wong, Gary" sort="Wong, Gary" uniqKey="Wong G" first="Gary" last="Wong">Gary Wong</name><affiliation wicri:level="1"><nlm:aff id="A2">Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2</wicri:regionArea><wicri:noRegion>Manitoba R3E 3R2</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A3">Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Gren, Jason" sort="Gren, Jason" uniqKey="Gren J" first="Jason" last="Gren">Jason Gren</name><affiliation wicri:level="1"><nlm:aff id="A2">Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2</wicri:regionArea><wicri:noRegion>Manitoba R3E 3R2</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A3">Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Kobasa, Darwyn" sort="Kobasa, Darwyn" uniqKey="Kobasa D" first="Darwyn" last="Kobasa">Darwyn Kobasa</name><affiliation wicri:level="1"><nlm:aff id="A2">Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2</wicri:regionArea><wicri:noRegion>Manitoba R3E 3R2</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A3">Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Ross, Ted M" sort="Ross, Ted M" uniqKey="Ross T" first="Ted M." last="Ross">Ted M. Ross</name><affiliation wicri:level="4"><nlm:aff id="A4">Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="A5">Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Kobinger, Gary P" sort="Kobinger, Gary P" uniqKey="Kobinger G" first="Gary P." last="Kobinger">Gary P. Kobinger</name><affiliation wicri:level="1"><nlm:aff id="A2">Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2</wicri:regionArea><wicri:noRegion>Manitoba R3E 3R2</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A3">Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A6">Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Tretiakova, Anna" sort="Tretiakova, Anna" uniqKey="Tretiakova A" first="Anna" last="Tretiakova">Anna Tretiakova</name><affiliation wicri:level="2"><nlm:aff id="A1">Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Wilson, James M" sort="Wilson, James M" uniqKey="Wilson J" first="James M." last="Wilson">James M. Wilson</name><affiliation wicri:level="2"><nlm:aff id="A1">Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></analytic><series><title level="j">Science translational medicine</title><idno type="ISSN">1946-6234</idno><idno type="eISSN">1946-6242</idno><imprint><date when="2013">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"><p id="P1">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 LD<sub>50</sub> (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.</p></div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Manitoba</li><li>Pennsylvanie</li></region><settlement><li>Pittsburgh</li><li>Winnipeg</li></settlement><orgName><li>Université de Pittsburgh</li><li>Université du Manitoba</li></orgName></list><tree><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><name sortKey="Adam, Virginie S" sort="Adam, Virginie S" uniqKey="Adam V" first="Virginie S." last="Adam">Virginie S. Adam</name><name sortKey="Ross, Ted M" sort="Ross, Ted M" uniqKey="Ross T" first="Ted M." last="Ross">Ted M. Ross</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></country><country name="Canada"><noRegion><name sortKey="Wong, Gary" sort="Wong, Gary" uniqKey="Wong G" first="Gary" last="Wong">Gary Wong</name></noRegion><name sortKey="Gren, Jason" sort="Gren, Jason" uniqKey="Gren J" first="Jason" last="Gren">Jason Gren</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="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="Kobinger, Gary P" sort="Kobinger, Gary P" uniqKey="Kobinger G" first="Gary P." last="Kobinger">Gary P. Kobinger</name><name sortKey="Kobinger, Gary P" sort="Kobinger, Gary P" uniqKey="Kobinger G" first="Gary P." last="Kobinger">Gary P. Kobinger</name><name sortKey="Wong, Gary" sort="Wong, Gary" uniqKey="Wong G" first="Gary" last="Wong">Gary Wong</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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