Broadly Reactive Human Monoclonal Antibodies Elicited following Pandemic H1N1 Influenza Virus Exposure Protect Mice against Highly Pathogenic H5N1 Challenge
Identifieur interne : 000163 ( Pmc/Checkpoint ); précédent : 000162; suivant : 000164Broadly Reactive Human Monoclonal Antibodies Elicited following Pandemic H1N1 Influenza Virus Exposure Protect Mice against Highly Pathogenic H5N1 Challenge
Auteurs : Raffael Nachbagauer [États-Unis] ; David Shore [États-Unis] ; Hua Yang [États-Unis] ; Scott K. Johnson [États-Unis] ; Jon D. Gabbard [États-Unis] ; S. Mark Tompkins [États-Unis] ; Jens Wrammert [États-Unis] ; Patrick C. Wilson [États-Unis] ; James Stevens [États-Unis] ; Rafi Ahmed [États-Unis] ; Florian Krammer [États-Unis] ; Ali H. Ellebedy [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2018.
Abstract
The rise in zoonotic infections of humans by emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually worldwide. Currently available antiviral treatment options include only neuraminidase inhibitors, but some influenza viruses are naturally resistant to these drugs, and others quickly develop resistance-conferring mutations. Alternative therapeutics are urgently needed. Broadly protective antibodies that target the conserved “stalk” domain of the hemagglutinin represent potential potent antiviral prophylactic and therapeutic agents that can assist pandemic preparedness. Here, we describe four human monoclonal antibodies that target conserved regions of influenza HA and characterize their binding spectrum as well as their protective capacity in prophylactic and therapeutic settings against a lethal challenge with a zoonotic influenza virus.
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DOI: 10.1128/JVI.00949-18
PubMed: 29899095
PubMed Central: 6069173
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Broadly Reactive Human Monoclonal Antibodies Elicited following Pandemic H1N1 Influenza Virus Exposure Protect Mice against Highly Pathogenic H5N1 Challenge</title><author><name sortKey="Nachbagauer, Raffael" sort="Nachbagauer, Raffael" uniqKey="Nachbagauer R" first="Raffael" last="Nachbagauer">Raffael Nachbagauer</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Shore, David" sort="Shore, David" uniqKey="Shore D" first="David" last="Shore">David Shore</name><affiliation wicri:level="2"><nlm:aff id="aff2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Yang, Hua" sort="Yang, Hua" uniqKey="Yang H" first="Hua" last="Yang">Hua Yang</name><affiliation wicri:level="2"><nlm:aff id="aff2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Johnson, Scott K" sort="Johnson, Scott K" uniqKey="Johnson S" first="Scott K." last="Johnson">Scott K. Johnson</name><affiliation wicri:level="2"><nlm:aff id="aff3">Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Gabbard, Jon D" sort="Gabbard, Jon D" uniqKey="Gabbard J" first="Jon D." last="Gabbard">Jon D. Gabbard</name><affiliation wicri:level="2"><nlm:aff id="aff3">Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Tompkins, S Mark" sort="Tompkins, S Mark" uniqKey="Tompkins S" first="S. Mark" last="Tompkins">S. Mark Tompkins</name><affiliation wicri:level="2"><nlm:aff id="aff3">Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Wrammert, Jens" sort="Wrammert, Jens" uniqKey="Wrammert J" first="Jens" last="Wrammert">Jens Wrammert</name><affiliation wicri:level="2"><nlm:aff id="aff4">Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Wilson, Patrick C" sort="Wilson, Patrick C" uniqKey="Wilson P" first="Patrick C." last="Wilson">Patrick C. Wilson</name><affiliation wicri:level="4"><nlm:aff id="aff5">Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name><affiliation wicri:level="2"><nlm:aff id="aff2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Ahmed, Rafi" sort="Ahmed, Rafi" uniqKey="Ahmed R" first="Rafi" last="Ahmed">Rafi Ahmed</name><affiliation wicri:level="2"><nlm:aff id="aff4">Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff6">Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Krammer, Florian" sort="Krammer, Florian" uniqKey="Krammer F" first="Florian" last="Krammer">Florian Krammer</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Ellebedy, Ali H" sort="Ellebedy, Ali H" uniqKey="Ellebedy A" first="Ali H." last="Ellebedy">Ali H. Ellebedy</name><affiliation wicri:level="2"><nlm:aff id="aff4">Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff6">Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29899095</idno><idno type="pmc">6069173</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069173</idno><idno type="RBID">PMC:6069173</idno><idno type="doi">10.1128/JVI.00949-18</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000705</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000705</idno><idno type="wicri:Area/Pmc/Curation">000705</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000705</idno><idno type="wicri:Area/Pmc/Checkpoint">000163</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000163</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Broadly Reactive Human Monoclonal Antibodies Elicited following Pandemic H1N1 Influenza Virus Exposure Protect Mice against Highly Pathogenic H5N1 Challenge</title><author><name sortKey="Nachbagauer, Raffael" sort="Nachbagauer, Raffael" uniqKey="Nachbagauer R" first="Raffael" last="Nachbagauer">Raffael Nachbagauer</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Shore, David" sort="Shore, David" uniqKey="Shore D" first="David" last="Shore">David Shore</name><affiliation wicri:level="2"><nlm:aff id="aff2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Yang, Hua" sort="Yang, Hua" uniqKey="Yang H" first="Hua" last="Yang">Hua Yang</name><affiliation wicri:level="2"><nlm:aff id="aff2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Johnson, Scott K" sort="Johnson, Scott K" uniqKey="Johnson S" first="Scott K." last="Johnson">Scott K. Johnson</name><affiliation wicri:level="2"><nlm:aff id="aff3">Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Gabbard, Jon D" sort="Gabbard, Jon D" uniqKey="Gabbard J" first="Jon D." last="Gabbard">Jon D. Gabbard</name><affiliation wicri:level="2"><nlm:aff id="aff3">Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Tompkins, S Mark" sort="Tompkins, S Mark" uniqKey="Tompkins S" first="S. Mark" last="Tompkins">S. Mark Tompkins</name><affiliation wicri:level="2"><nlm:aff id="aff3">Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Wrammert, Jens" sort="Wrammert, Jens" uniqKey="Wrammert J" first="Jens" last="Wrammert">Jens Wrammert</name><affiliation wicri:level="2"><nlm:aff id="aff4">Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Wilson, Patrick C" sort="Wilson, Patrick C" uniqKey="Wilson P" first="Patrick C." last="Wilson">Patrick C. Wilson</name><affiliation wicri:level="4"><nlm:aff id="aff5">Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name><affiliation wicri:level="2"><nlm:aff id="aff2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Ahmed, Rafi" sort="Ahmed, Rafi" uniqKey="Ahmed R" first="Rafi" last="Ahmed">Rafi Ahmed</name><affiliation wicri:level="2"><nlm:aff id="aff4">Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff6">Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Krammer, Florian" sort="Krammer, Florian" uniqKey="Krammer F" first="Florian" last="Krammer">Florian Krammer</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Ellebedy, Ali H" sort="Ellebedy, Ali H" uniqKey="Ellebedy A" first="Ali H." last="Ellebedy">Ali H. Ellebedy</name><affiliation wicri:level="2"><nlm:aff id="aff4">Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff6">Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The rise in zoonotic infections of humans by emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually worldwide. Currently available antiviral treatment options include only neuraminidase inhibitors, but some influenza viruses are naturally resistant to these drugs, and others quickly develop resistance-conferring mutations. Alternative therapeutics are urgently needed. Broadly protective antibodies that target the conserved “stalk” domain of the hemagglutinin represent potential potent antiviral prophylactic and therapeutic agents that can assist pandemic preparedness. Here, we describe four human monoclonal antibodies that target conserved regions of influenza HA and characterize their binding spectrum as well as their protective capacity in prophylactic and therapeutic settings against a lethal challenge with a zoonotic influenza virus.</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>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id><journal-id journal-id-type="iso-abbrev">J. Virol</journal-id><journal-id journal-id-type="hwp">jvi</journal-id><journal-id journal-id-type="pmc">jvi</journal-id><journal-id journal-id-type="publisher-id">JVI</journal-id><journal-title-group><journal-title>Journal of Virology</journal-title></journal-title-group><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology</publisher-name><publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29899095</article-id><article-id pub-id-type="pmc">6069173</article-id><article-id pub-id-type="publisher-id">00949-18</article-id><article-id pub-id-type="doi">10.1128/JVI.00949-18</article-id><article-categories><subj-group subj-group-type="heading"><subject>Vaccines and Antiviral Agents</subject></subj-group></article-categories><title-group><article-title>Broadly Reactive Human Monoclonal Antibodies Elicited following Pandemic H1N1 Influenza Virus Exposure Protect Mice against Highly Pathogenic H5N1 Challenge</article-title><alt-title alt-title-type="running-head"><italic>In Vivo</italic> Protective Human Influenza HA Stalk Antibodies</alt-title><alt-title alt-title-type="short-authors">Nachbagauer et al.</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0001-5568-5420</contrib-id><name><surname>Nachbagauer</surname><given-names>Raffael</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Shore</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Yang</surname><given-names>Hua</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Johnson</surname><given-names>Scott K.</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Gabbard</surname><given-names>Jon D.</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0002-1523-5588</contrib-id><name><surname>Tompkins</surname><given-names>S. Mark</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Wrammert</surname><given-names>Jens</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Wilson</surname><given-names>Patrick C.</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Stevens</surname><given-names>James</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Ahmed</surname><given-names>Rafi</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author" corresp="yes" equal-contrib="no"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0003-4121-776X</contrib-id><name><surname>Krammer</surname><given-names>Florian</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" corresp="yes" equal-contrib="no"><name><surname>Ellebedy</surname><given-names>Ali H.</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><aff id="aff1"><label>a</label>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</aff><aff id="aff2"><label>b</label>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA</aff><aff id="aff3"><label>c</label>Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA</aff><aff id="aff4"><label>d</label>Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA</aff><aff id="aff5"><label>e</label>Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois, USA</aff><aff id="aff6"><label>f</label>Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA</aff></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Schultz-Cherry</surname><given-names>Stacey</given-names></name><role>Editor</role><aff>St. Jude Children's Research Hospital</aff></contrib></contrib-group><author-notes><corresp id="cor1">Address correspondence to Florian Krammer, <email>florian.krammer@mssm.edu</email>, or Ali H. Ellebedy, <email>ellebedy@wustl.edu</email>.</corresp><fn id="fn1" fn-type="present-address"><label>*</label><p>Present address: Ali H. Ellebedy, Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.</p></fn><fn fn-type="equal"><p>R.N. and D.S. contributed equally to this article.</p></fn><fn fn-type="other"><p><bold>Citation</bold> Nachbagauer R, Shore D, Yang H, Johnson SK, Gabbard JD, Tompkins SM, Wrammert J, Wilson PC, Stevens J, Ahmed R, Krammer F, Ellebedy AH. 2018. Broadly reactive human monoclonal antibodies elicited following pandemic H1N1 influenza virus exposure protect mice against highly pathogenic H5N1 challenge. J Virol 92:e00949-18. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/JVI.00949-18">https://doi.org/10.1128/JVI.00949-18</ext-link>.</p></fn></author-notes><pub-date pub-type="epreprint"><day>13</day><month>6</month><year>2018</year></pub-date><pub-date pub-type="epub"><day>31</day><month>7</month><year>2018</year></pub-date><pub-date pub-type="collection"><day>15</day><month>8</month><year>2018</year></pub-date><volume>92</volume><issue>16</issue><elocation-id>e00949-18</elocation-id><history><date date-type="received"><day>30</day><month>5</month><year>2018</year></date><date date-type="accepted"><day>2</day><month>6</month><year>2018</year></date></history><permissions><copyright-statement>Copyright © 2018 American Society for Microbiology.</copyright-statement><copyright-year>2018</copyright-year><copyright-holder>American Society for Microbiology</copyright-holder><license license-type="asm" xlink:href="https://doi.org/10.1128/ASMCopyrightv2"><license-p><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/ASMCopyrightv2">All Rights Reserved</ext-link>.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="zjv016183788001.pdf"></self-uri><abstract abstract-type="precis"><p>The rise in zoonotic infections of humans by emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually worldwide. Currently available antiviral treatment options include only neuraminidase inhibitors, but some influenza viruses are naturally resistant to these drugs, and others quickly develop resistance-conferring mutations. Alternative therapeutics are urgently needed. Broadly protective antibodies that target the conserved “stalk” domain of the hemagglutinin represent potential potent antiviral prophylactic and therapeutic agents that can assist pandemic preparedness. Here, we describe four human monoclonal antibodies that target conserved regions of influenza HA and characterize their binding spectrum as well as their protective capacity in prophylactic and therapeutic settings against a lethal challenge with a zoonotic influenza virus.</p></abstract><abstract><title>ABSTRACT</title><p>Broadly cross-reactive antibodies (Abs) that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes, including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (MAbs) for their binding breadth and affinity, <italic>in vitro</italic> neutralization capacity, and <italic>in vivo</italic> protective potential against an highly pathogenic avian influenza virus. The monoclonal antibodies were isolated from individuals shortly following infection with (70-1F02 and 1009-3B05) or vaccination against (05-2G02 and 09-3A01) A(H1N1)pdm09. Three of the MAbs bound HAs from multiple strains of group 1 viruses, and one MAb, 05-2G02, bound to both group 1 and group 2 influenza A virus HAs. All four antibodies prophylactically protected mice against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) strain. Two MAbs, 70-1F02 and 09-3A01, were further tested for their therapeutic efficacy against the same strain and showed good efficacy in this setting as well. One MAb, 70-1F02, cocrystallized with H5 HA and showed heavy-chain-only interactions similar to those seen with the previously described CR6261 anti-stalk antibody. Finally, we show that antibodies that compete with these MAbs are prevalent in serum from an individual recently infected with the A(H1N1)pdm09 virus. The antibodies described here can be developed into broad-spectrum antiviral therapeutics that could be used to combat infections by zoonotic or emerging pandemic influenza viruses.</p><p><bold>IMPORTANCE</bold> The rise in zoonotic infections of humans by emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually worldwide. Currently available antiviral treatment options include only neuraminidase inhibitors, but some influenza viruses are naturally resistant to these drugs, and others quickly develop resistance-conferring mutations. Alternative therapeutics are urgently needed. Broadly protective antibodies that target the conserved “stalk” domain of the hemagglutinin represent potential potent antiviral prophylactic and therapeutic agents that can assist pandemic preparedness. Here, we describe four human monoclonal antibodies that target conserved regions of influenza HA and characterize their binding spectrum as well as their protective capacity in prophylactic and therapeutic settings against a lethal challenge with a zoonotic influenza virus.</p></abstract><kwd-group><title>KEYWORDS</title><kwd>H5N1</kwd><kwd>HA stalk</kwd><kwd>hemagglutinin</kwd><kwd>hemagglutinin stalk</kwd><kwd>influenza</kwd><kwd>influenza virus</kwd><kwd>monoclonal antibody</kwd></kwd-group><funding-group><award-group id="award1"><funding-source id="gs1"><institution-wrap><institution>HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)</institution><institution-id>https://doi.org/10.13039/100000060</institution-id></institution-wrap></funding-source><award-id rid="gs1">AI109946</award-id><award-id rid="gs1">HHSN272201400008C</award-id><principal-award-recipient><name><surname>Krammer</surname><given-names>Florian</given-names></name></principal-award-recipient><principal-award-recipient><name><surname>Ellebedy</surname><given-names>Ali H.</given-names></name></principal-award-recipient></award-group><award-group id="award2"><funding-source id="gs2"><institution-wrap><institution>HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)</institution><institution-id>https://doi.org/10.13039/100000060</institution-id></institution-wrap></funding-source><award-id rid="gs2">HHSN266200700006C</award-id><award-id rid="gs2">HHSN272201400004C</award-id><principal-award-recipient><name><surname>Ahmed</surname><given-names>Rafi</given-names></name></principal-award-recipient></award-group></funding-group><counts><fig-count count="7"></fig-count><table-count count="3"></table-count><equation-count count="0"></equation-count><ref-count count="75"></ref-count><page-count count="17"></page-count><word-count count="11865"></word-count></counts><custom-meta-group><custom-meta><meta-name>cover-date</meta-name><meta-value>August 2018</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>États-Unis</li></country><region><li>Géorgie (États-Unis)</li><li>Illinois</li><li>État de New York</li></region><settlement><li>Chicago</li></settlement><orgName><li>Université de Chicago</li></orgName></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Nachbagauer, Raffael" sort="Nachbagauer, Raffael" uniqKey="Nachbagauer R" first="Raffael" last="Nachbagauer">Raffael Nachbagauer</name></region><name sortKey="Ahmed, Rafi" sort="Ahmed, Rafi" uniqKey="Ahmed R" first="Rafi" last="Ahmed">Rafi Ahmed</name><name sortKey="Ahmed, Rafi" sort="Ahmed, Rafi" uniqKey="Ahmed R" first="Rafi" last="Ahmed">Rafi Ahmed</name><name sortKey="Ellebedy, Ali H" sort="Ellebedy, Ali H" uniqKey="Ellebedy A" first="Ali H." last="Ellebedy">Ali H. Ellebedy</name><name sortKey="Ellebedy, Ali H" sort="Ellebedy, Ali H" uniqKey="Ellebedy A" first="Ali H." last="Ellebedy">Ali H. Ellebedy</name><name sortKey="Gabbard, Jon D" sort="Gabbard, Jon D" uniqKey="Gabbard J" first="Jon D." last="Gabbard">Jon D. Gabbard</name><name sortKey="Johnson, Scott K" sort="Johnson, Scott K" uniqKey="Johnson S" first="Scott K." last="Johnson">Scott K. Johnson</name><name sortKey="Krammer, Florian" sort="Krammer, Florian" uniqKey="Krammer F" first="Florian" last="Krammer">Florian Krammer</name><name sortKey="Shore, David" sort="Shore, David" uniqKey="Shore D" first="David" last="Shore">David Shore</name><name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name><name sortKey="Tompkins, S Mark" sort="Tompkins, S Mark" uniqKey="Tompkins S" first="S. Mark" last="Tompkins">S. Mark Tompkins</name><name sortKey="Wilson, Patrick C" sort="Wilson, Patrick C" uniqKey="Wilson P" first="Patrick C." last="Wilson">Patrick C. Wilson</name><name sortKey="Wrammert, Jens" sort="Wrammert, Jens" uniqKey="Wrammert J" first="Jens" last="Wrammert">Jens Wrammert</name><name sortKey="Yang, Hua" sort="Yang, Hua" uniqKey="Yang H" first="Hua" last="Yang">Hua Yang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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