A Human Antibody Recognizing a Conserved Epitope of H5 Hemagglutinin Broadly Neutralizes Highly Pathogenic Avian Influenza H5N1 Viruses
Identifieur interne : 000A94 ( Main/Exploration ); précédent : 000A93; suivant : 000A95A Human Antibody Recognizing a Conserved Epitope of H5 Hemagglutinin Broadly Neutralizes Highly Pathogenic Avian Influenza H5N1 Viruses
Auteurs : Hongxing Hu [République populaire de Chine] ; Jarrod Voss [Royaume-Uni] ; Guoliang Zhang [République populaire de Chine] ; Philippi Buchy [Cambodge] ; Teng Zuo [République populaire de Chine] ; Lulan Wang [République populaire de Chine] ; Feng Wang [République populaire de Chine] ; Fan Zhou [République populaire de Chine] ; Guiqing Wang [République populaire de Chine] ; Cheguo Tsai [République populaire de Chine] ; Lesley Calder [Royaume-Uni] ; Steve J. Gamblin [Royaume-Uni] ; Linqi Zhang [République populaire de Chine] ; Vincent Deubel [Cambodge] ; Boping Zhou [République populaire de Chine] ; John J. Skehel [Royaume-Uni] ; Paul Zhou [République populaire de Chine]Source :
- Journal of Virology [ 0022-538X ] ; 2012.
Abstract
Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are similar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from an H5N1-infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at positions 118, 121, 161, 164, and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains.
Url:
DOI: 10.1128/JVI.06665-11
PubMed: 22238297
PubMed Central: 3302345
Affiliations:
- Cambodge, Royaume-Uni, République populaire de Chine
- Angleterre, Grand Londres, Guangdong
- Londres, Pékin, Shenzhen
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000644
- to stream Pmc, to step Curation: 000644
- to stream Pmc, to step Checkpoint: 000761
- to stream Ncbi, to step Merge: 000729
- to stream Ncbi, to step Curation: 000729
- to stream Ncbi, to step Checkpoint: 000729
- to stream Main, to step Merge: 000A97
- to stream Main, to step Curation: 000A94
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Human Antibody Recognizing a Conserved Epitope of H5 Hemagglutinin Broadly Neutralizes Highly Pathogenic Avian Influenza H5N1 Viruses</title><author><name sortKey="Hu, Hongxing" sort="Hu, Hongxing" uniqKey="Hu H" first="Hongxing" last="Hu">Hongxing Hu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Voss, Jarrod" sort="Voss, Jarrod" uniqKey="Voss J" first="Jarrod" last="Voss">Jarrod 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Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Feng" sort="Wang, Feng" uniqKey="Wang F" first="Feng" last="Wang">Feng Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Fan" sort="Zhou, Fan" uniqKey="Zhou F" first="Fan" last="Zhou">Fan Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Guiqing" sort="Wang, Guiqing" uniqKey="Wang G" first="Guiqing" last="Wang">Guiqing Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Tsai, Cheguo" sort="Tsai, Cheguo" uniqKey="Tsai C" first="Cheguo" last="Tsai">Cheguo Tsai</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Calder, Lesley" sort="Calder, Lesley" uniqKey="Calder L" first="Lesley" last="Calder">Lesley Calder</name><affiliation wicri:level="3"><nlm:aff id="aff2">National Institute for Medical Research, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Medical Research, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Gamblin, Steve J" sort="Gamblin, Steve J" uniqKey="Gamblin S" 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Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Voss, Jarrod" sort="Voss, Jarrod" uniqKey="Voss J" first="Jarrod" last="Voss">Jarrod Voss</name><affiliation wicri:level="3"><nlm:aff id="aff2">National Institute for Medical Research, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Medical Research, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Zhang, Guoliang" sort="Zhang, Guoliang" uniqKey="Zhang G" first="Guoliang" last="Zhang">Guoliang Zhang</name><affiliation wicri:level="3"><nlm:aff id="aff3">Shenzhen Third Hospital, Shenzhen, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenzhen Third Hospital, Shenzhen</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Buchy, Philippi" sort="Buchy, Philippi" uniqKey="Buchy P" first="Philippi" last="Buchy">Philippi Buchy</name><affiliation wicri:level="1"><nlm:aff id="aff4">Institut Pasteur in Cambodia, Phnom Penh, Cambodia</nlm:aff><country xml:lang="fr">Cambodge</country><wicri:regionArea>Institut Pasteur in Cambodia, Phnom Penh</wicri:regionArea><wicri:noRegion>Phnom Penh</wicri:noRegion></affiliation></author><author><name sortKey="Zuo, Teng" sort="Zuo, Teng" uniqKey="Zuo T" first="Teng" last="Zuo">Teng Zuo</name><affiliation wicri:level="3"><nlm:aff id="aff5">Comprehensive AIDS Research Center, School of Medicine, Tsinghua University, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, School of Medicine, Tsinghua University, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Lulan" sort="Wang, Lulan" uniqKey="Wang L" first="Lulan" last="Wang">Lulan Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Feng" sort="Wang, Feng" uniqKey="Wang F" first="Feng" last="Wang">Feng Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Fan" sort="Zhou, Fan" uniqKey="Zhou F" first="Fan" last="Zhou">Fan Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Guiqing" sort="Wang, Guiqing" uniqKey="Wang G" first="Guiqing" last="Wang">Guiqing Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Tsai, Cheguo" sort="Tsai, Cheguo" uniqKey="Tsai C" first="Cheguo" last="Tsai">Cheguo Tsai</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Calder, Lesley" sort="Calder, Lesley" uniqKey="Calder L" first="Lesley" last="Calder">Lesley Calder</name><affiliation wicri:level="3"><nlm:aff id="aff2">National Institute for Medical Research, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Medical Research, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Gamblin, Steve J" sort="Gamblin, Steve J" uniqKey="Gamblin S" first="Steve J." last="Gamblin">Steve J. Gamblin</name><affiliation wicri:level="3"><nlm:aff id="aff2">National Institute for Medical Research, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Medical Research, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><affiliation wicri:level="3"><nlm:aff id="aff5">Comprehensive AIDS Research Center, School of Medicine, Tsinghua University, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, School of Medicine, Tsinghua University, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Deubel, Vincent" sort="Deubel, Vincent" uniqKey="Deubel V" first="Vincent" last="Deubel">Vincent Deubel</name><affiliation wicri:level="1"><nlm:aff id="aff4">Institut Pasteur in Cambodia, Phnom Penh, Cambodia</nlm:aff><country xml:lang="fr">Cambodge</country><wicri:regionArea>Institut Pasteur in Cambodia, Phnom Penh</wicri:regionArea><wicri:noRegion>Phnom Penh</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Boping" sort="Zhou, Boping" uniqKey="Zhou B" first="Boping" last="Zhou">Boping Zhou</name><affiliation wicri:level="3"><nlm:aff id="aff3">Shenzhen Third Hospital, Shenzhen, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenzhen Third Hospital, Shenzhen</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Skehel, John J" sort="Skehel, John J" uniqKey="Skehel J" first="John J." last="Skehel">John J. Skehel</name><affiliation wicri:level="3"><nlm:aff id="aff2">National Institute for Medical Research, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Medical Research, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Zhou, Paul" sort="Zhou, Paul" uniqKey="Zhou P" first="Paul" last="Zhou">Paul Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff1">Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></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="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are similar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from an H5N1-infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at positions 118, 121, 161, 164, and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains.</p></div></front></TEI><affiliations><list><country><li>Cambodge</li><li>Royaume-Uni</li><li>République populaire de Chine</li></country><region><li>Angleterre</li><li>Grand Londres</li><li>Guangdong</li></region><settlement><li>Londres</li><li>Pékin</li><li>Shenzhen</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Hu, Hongxing" sort="Hu, Hongxing" uniqKey="Hu H" first="Hongxing" last="Hu">Hongxing Hu</name></noRegion><name sortKey="Tsai, Cheguo" sort="Tsai, Cheguo" uniqKey="Tsai C" first="Cheguo" last="Tsai">Cheguo Tsai</name><name sortKey="Wang, Feng" sort="Wang, Feng" uniqKey="Wang F" first="Feng" last="Wang">Feng Wang</name><name sortKey="Wang, Guiqing" sort="Wang, Guiqing" uniqKey="Wang G" first="Guiqing" last="Wang">Guiqing Wang</name><name sortKey="Wang, Lulan" sort="Wang, Lulan" uniqKey="Wang L" first="Lulan" last="Wang">Lulan Wang</name><name sortKey="Zhang, Guoliang" sort="Zhang, Guoliang" uniqKey="Zhang G" first="Guoliang" last="Zhang">Guoliang Zhang</name><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><name sortKey="Zhou, Boping" sort="Zhou, Boping" uniqKey="Zhou B" first="Boping" last="Zhou">Boping Zhou</name><name sortKey="Zhou, Fan" sort="Zhou, Fan" uniqKey="Zhou F" first="Fan" last="Zhou">Fan Zhou</name><name sortKey="Zhou, Paul" sort="Zhou, Paul" uniqKey="Zhou P" first="Paul" last="Zhou">Paul Zhou</name><name sortKey="Zuo, Teng" sort="Zuo, Teng" uniqKey="Zuo T" first="Teng" last="Zuo">Teng Zuo</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Voss, Jarrod" sort="Voss, Jarrod" uniqKey="Voss J" first="Jarrod" last="Voss">Jarrod Voss</name></region><name sortKey="Calder, Lesley" sort="Calder, Lesley" uniqKey="Calder L" first="Lesley" last="Calder">Lesley Calder</name><name sortKey="Gamblin, Steve J" sort="Gamblin, Steve J" uniqKey="Gamblin S" first="Steve J." last="Gamblin">Steve J. Gamblin</name><name sortKey="Skehel, John J" sort="Skehel, John J" uniqKey="Skehel J" first="John J." last="Skehel">John J. Skehel</name></country><country name="Cambodge"><noRegion><name sortKey="Buchy, Philippi" sort="Buchy, Philippi" uniqKey="Buchy P" first="Philippi" last="Buchy">Philippi Buchy</name></noRegion><name sortKey="Deubel, Vincent" sort="Deubel, Vincent" uniqKey="Deubel V" first="Vincent" last="Deubel">Vincent Deubel</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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