Broadly Reactive Human Monoclonal Antibodies Elicited following Pandemic H1N1 Influenza Virus Exposure Protect Mice against Highly Pathogenic H5N1 Challenge
Identifieur interne : 000215 ( Main/Exploration ); précédent : 000214; suivant : 000216Broadly 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.
Url:
DOI: 10.1128/JVI.00949-18
PubMed: 29899095
PubMed Central: 6069173
Affiliations:
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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. 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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><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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