Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza
Identifieur interne : 000839 ( Pmc/Curation ); précédent : 000838; suivant : 000840Intranasal 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.
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.
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DOI: 10.1126/scitranslmed.3006299
PubMed: 23720583
PubMed Central: 4596530
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Adam</name><affiliation wicri:level="1"><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></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></affiliation><affiliation wicri:level="1"><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></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></affiliation><affiliation wicri:level="1"><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></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></affiliation><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Ross, Ted M" sort="Ross, Ted M" uniqKey="Ross T" first="Ted M." last="Ross">Ted M. 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Wilson</name><affiliation wicri:level="1"><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></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23720583</idno><idno type="pmc">4596530</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596530</idno><idno type="RBID">PMC:4596530</idno><idno type="doi">10.1126/scitranslmed.3006299</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000839</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000839</idno><idno type="wicri:Area/Pmc/Curation">000839</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000839</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza</title><author><name sortKey="Limberis, Maria P" sort="Limberis, Maria P" uniqKey="Limberis M" first="Maria P." last="Limberis">Maria P. Limberis</name><affiliation wicri:level="1"><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></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="1"><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></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></affiliation><affiliation wicri:level="1"><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></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></affiliation><affiliation wicri:level="1"><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></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></affiliation><affiliation wicri:level="1"><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></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="1"><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></affiliation><affiliation wicri:level="1"><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></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></affiliation><affiliation wicri:level="1"><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></affiliation><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Tretiakova, Anna" sort="Tretiakova, Anna" uniqKey="Tretiakova A" first="Anna" last="Tretiakova">Anna Tretiakova</name><affiliation wicri:level="1"><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></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="1"><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></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></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><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101505086</journal-id><journal-id journal-id-type="pubmed-jr-id">36963</journal-id><journal-id journal-id-type="nlm-ta">Sci Transl Med</journal-id><journal-id journal-id-type="iso-abbrev">Sci Transl Med</journal-id><journal-title-group><journal-title>Science translational medicine</journal-title></journal-title-group><issn pub-type="ppub">1946-6234</issn><issn pub-type="epub">1946-6242</issn></journal-meta><article-meta><article-id pub-id-type="pmid">23720583</article-id><article-id pub-id-type="pmc">4596530</article-id><article-id pub-id-type="doi">10.1126/scitranslmed.3006299</article-id><article-id pub-id-type="manuscript">NIHMS686805</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Limberis</surname><given-names>Maria P.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN1" ref-type="author-notes">*</xref><xref rid="FN2" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Adam</surname><given-names>Virginie S.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Wong</surname><given-names>Gary</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Gren</surname><given-names>Jason</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Kobasa</surname><given-names>Darwyn</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ross</surname><given-names>Ted M.</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Kobinger</surname><given-names>Gary P.</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Tretiakova</surname><given-names>Anna</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Wilson</surname><given-names>James M.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN1" ref-type="author-notes">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104, USA</aff><aff id="A2"><label>2</label>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada</aff><aff id="A3"><label>3</label>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada</aff><aff id="A4"><label>4</label>Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA</aff><aff id="A5"><label>5</label>Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA</aff><aff id="A6"><label>6</label>Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada</aff><author-notes><corresp id="FN1"><label>*</label>Corresponding author. <email>limberis@mail.med.upenn.edu</email> (M.P.L.); <email>wilsonjm@mail.med.upenn.edu</email> (J.M.W.)</corresp><fn id="FN2" fn-type="equal"><label>†</label><p>These authors contributed equally to this work.</p></fn><fn id="FN5" fn-type="conflict"><p><bold>Competing interests:</bold> J.M.W. is a consultant to ReGenX Holdings and is a founder of, holds equity in, and receives a grant from affiliates of ReGenX Holdings; in addition, relevant to this work, he is an inventor on patents licensed to various biopharmaceutical companies, including affiliates of ReGenX Holdings. The other authors declare no competing interests. J.M.W. holds a patent on adeno-associated virus (AAV) clades (U.S. Patent 7,906,111B2) with pending continuation (U.S. Patent 13/023,918). J.M.W. and M.P.L. have a pending application on AAV-mediated passive immunization of airborne pathogens (PCT/US2012/034355).</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>5</day><month>5</month><year>2015</year></pub-date><pub-date pub-type="ppub"><day>29</day><month>5</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>07</day><month>10</month><year>2015</year></pub-date><volume>5</volume><issue>187</issue><fpage>187ra72</fpage><lpage>187ra72</lpage><pmc-comment>elocation-id from pubmed: 10.1126/scitranslmed.3006299</pmc-comment>
<abstract><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></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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