A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus
Identifieur interne : 003C47 ( Main/Curation ); précédent : 003C46; suivant : 003C48A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus
Auteurs : Wanwisa Dejnirattisai [Royaume-Uni] ; Wiyada Wongwiwat [Royaume-Uni] ; Sunpetchuda Supasa [Royaume-Uni, Thaïlande] ; Xiaokang Zhang [France] ; Xinghong Dai [États-Unis] ; Alexander Rouvinski [France] ; Amonrat Jumnainsong [Royaume-Uni, Thaïlande] ; Carolyn Edwards [Royaume-Uni] ; Nguyen Than Ha Quyen [Viêt Nam] ; Thaneeya Duangchinda [Thaïlande] ; Jonathan M. Grimes [Royaume-Uni] ; Wen-Yang Tsai [États-Unis] ; Chih-Yun Lai [États-Unis] ; Wei-Kung Wang [États-Unis] ; Prida Malasit [Thaïlande] ; Jeremy Farrar [Viêt Nam] ; Cameron P. Simmons [Viêt Nam, Australie] ; Z Hong Zhou [États-Unis] ; Felix A. Rey [France] ; Juthathip Mongkolsapaya [Royaume-Uni, Thaïlande] ; Gavin R. Screaton [Royaume-Uni]Source :
- Nature immunology [ 1529-2908 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Anticorps monoclonaux (isolement et purification), Anticorps monoclonaux (métabolisme), Anticorps monoclonaux (sang), Anticorps neutralisants (isolement et purification), Anticorps neutralisants (sang), Dengue (immunologie), Dengue (sang), Dosage biologique, Humains, Immunotransfert, Lignée cellulaire, Protéines de l'enveloppe virale (immunologie), Protéines de l'enveloppe virale (métabolisme), Test ELISA, Virus de la dengue (immunologie).
- MESH :
- immunologie : Dengue, Protéines de l'enveloppe virale, Virus de la dengue.
- isolement et purification : Anticorps monoclonaux, Anticorps neutralisants.
- métabolisme : Anticorps monoclonaux, Protéines de l'enveloppe virale.
- sang : Anticorps monoclonaux, Anticorps neutralisants, Dengue.
- Animaux, Dosage biologique, Humains, Immunotransfert, Lignée cellulaire, Test ELISA.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (blood), Antibodies, Monoclonal (isolation & purification), Antibodies, Monoclonal (metabolism), Antibodies, Neutralizing (blood), Antibodies, Neutralizing (isolation & purification), Biological Assay, Cell Line, Dengue (blood), Dengue (immunology), Dengue Virus (immunology), Enzyme-Linked Immunosorbent Assay, Humans, Immunoblotting, Viral Envelope Proteins (immunology), Viral Envelope Proteins (metabolism).
- MESH :
- chemical , blood : Antibodies, Monoclonal, Antibodies, Neutralizing.
- chemical , immunology : Viral Envelope Proteins.
- chemical , isolation & purification : Antibodies, Monoclonal, Antibodies, Neutralizing.
- chemical , metabolism : Antibodies, Monoclonal, Viral Envelope Proteins.
- blood : Dengue.
- immunology : Dengue, Dengue Virus.
- Animals, Biological Assay, Cell Line, Enzyme-Linked Immunosorbent Assay, Humans, Immunoblotting.
Abstract
Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.
Url:
DOI: 10.1038/ni.3058
PubMed: 25501631
PubMed Central: 4445969
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PMC:4445969Le document en format XML
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<author><name sortKey="Zhou, Z Hong" sort="Zhou, Z Hong" uniqKey="Zhou Z" first="Z Hong" last="Zhou">Z Hong Zhou</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus</title>
<author><name sortKey="Dejnirattisai, Wanwisa" sort="Dejnirattisai, Wanwisa" uniqKey="Dejnirattisai W" first="Wanwisa" last="Dejnirattisai">Wanwisa Dejnirattisai</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, 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="Wongwiwat, Wiyada" sort="Wongwiwat, Wiyada" uniqKey="Wongwiwat W" first="Wiyada" last="Wongwiwat">Wiyada Wongwiwat</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, 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="Supasa, Sunpetchuda" sort="Supasa, Sunpetchuda" uniqKey="Supasa S" first="Sunpetchuda" last="Supasa">Sunpetchuda Supasa</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2">Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Graduate Program in Immunology, Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Graduate Program in Immunology, Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhang, Xiaokang" sort="Zhang, Xiaokang" uniqKey="Zhang X" first="Xiaokang" last="Zhang">Xiaokang Zhang</name>
<affiliation wicri:level="3"><nlm:aff id="A4">Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A5">CNRS UMR 3569 Virologie, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 3569 Virologie, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dai, Xinghong" sort="Dai, Xinghong" uniqKey="Dai X" first="Xinghong" last="Dai">Xinghong Dai</name>
<affiliation wicri:level="2"><nlm:aff id="A6">Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rouvinski, Alexander" sort="Rouvinski, Alexander" uniqKey="Rouvinski A" first="Alexander" last="Rouvinski">Alexander Rouvinski</name>
<affiliation wicri:level="3"><nlm:aff id="A4">Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A5">CNRS UMR 3569 Virologie, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 3569 Virologie, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jumnainsong, Amonrat" sort="Jumnainsong, Amonrat" uniqKey="Jumnainsong A" first="Amonrat" last="Jumnainsong">Amonrat Jumnainsong</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A7">The Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>The Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen</wicri:regionArea>
<wicri:noRegion>Khon Kaen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Edwards, Carolyn" sort="Edwards, Carolyn" uniqKey="Edwards C" first="Carolyn" last="Edwards">Carolyn Edwards</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, 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="Quyen, Nguyen Than Ha" sort="Quyen, Nguyen Than Ha" uniqKey="Quyen N" first="Nguyen Than Ha" last="Quyen">Nguyen Than Ha Quyen</name>
<affiliation wicri:level="1"><nlm:aff id="A8">Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam</nlm:aff>
<country xml:lang="fr">Viêt Nam</country>
<wicri:regionArea>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City</wicri:regionArea>
<wicri:noRegion>Ho Chi Minh City</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Duangchinda, Thaneeya" sort="Duangchinda, Thaneeya" uniqKey="Duangchinda T" first="Thaneeya" last="Duangchinda">Thaneeya Duangchinda</name>
<affiliation wicri:level="1"><nlm:aff id="A9">Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani</wicri:regionArea>
<wicri:noRegion>Pathumthani</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Grimes, Jonathan M" sort="Grimes, Jonathan M" uniqKey="Grimes J" first="Jonathan M" last="Grimes">Jonathan M. Grimes</name>
<affiliation wicri:level="4"><nlm:aff id="A10">Division of Structural Biology and Oxford Protein Production Facility, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Structural Biology and Oxford Protein Production Facility, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford</wicri:regionArea>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
<settlement type="city">Oxford</settlement>
</placeName>
<orgName type="university">Université d'Oxford</orgName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A11">Science Division, Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Science Division, Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire</wicri:regionArea>
<wicri:noRegion>Oxfordshire</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tsai, Wen Yang" sort="Tsai, Wen Yang" uniqKey="Tsai W" first="Wen-Yang" last="Tsai">Wen-Yang Tsai</name>
<affiliation wicri:level="2"><nlm:aff id="A12">Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii</wicri:regionArea>
<placeName><region type="state">Hawaï</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lai, Chih Yun" sort="Lai, Chih Yun" uniqKey="Lai C" first="Chih-Yun" last="Lai">Chih-Yun Lai</name>
<affiliation wicri:level="2"><nlm:aff id="A12">Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii</wicri:regionArea>
<placeName><region type="state">Hawaï</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Wei Kung" sort="Wang, Wei Kung" uniqKey="Wang W" first="Wei-Kung" last="Wang">Wei-Kung Wang</name>
<affiliation wicri:level="2"><nlm:aff id="A12">Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii</wicri:regionArea>
<placeName><region type="state">Hawaï</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Malasit, Prida" sort="Malasit, Prida" uniqKey="Malasit P" first="Prida" last="Malasit">Prida Malasit</name>
<affiliation wicri:level="1"><nlm:aff id="A2">Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A9">Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani</wicri:regionArea>
<wicri:noRegion>Pathumthani</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Farrar, Jeremy" sort="Farrar, Jeremy" uniqKey="Farrar J" first="Jeremy" last="Farrar">Jeremy Farrar</name>
<affiliation wicri:level="1"><nlm:aff id="A8">Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam</nlm:aff>
<country xml:lang="fr">Viêt Nam</country>
<wicri:regionArea>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City</wicri:regionArea>
<wicri:noRegion>Ho Chi Minh City</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Simmons, Cameron P" sort="Simmons, Cameron P" uniqKey="Simmons C" first="Cameron P" last="Simmons">Cameron P. Simmons</name>
<affiliation wicri:level="1"><nlm:aff id="A8">Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam</nlm:aff>
<country xml:lang="fr">Viêt Nam</country>
<wicri:regionArea>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City</wicri:regionArea>
<wicri:noRegion>Ho Chi Minh City</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A13">Department of Microbiology and Immunology, University of Melbourne, Carlton, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, Carlton, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zhou, Z Hong" sort="Zhou, Z Hong" uniqKey="Zhou Z" first="Z Hong" last="Zhou">Z Hong Zhou</name>
<affiliation wicri:level="2"><nlm:aff id="A6">Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rey, Felix A" sort="Rey, Felix A" uniqKey="Rey F" first="Felix A" last="Rey">Felix A. Rey</name>
<affiliation wicri:level="3"><nlm:aff id="A4">Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A5">CNRS UMR 3569 Virologie, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 3569 Virologie, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mongkolsapaya, Juthathip" sort="Mongkolsapaya, Juthathip" uniqKey="Mongkolsapaya J" first="Juthathip" last="Mongkolsapaya">Juthathip Mongkolsapaya</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2">Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Screaton, Gavin R" sort="Screaton, Gavin R" uniqKey="Screaton G" first="Gavin R" last="Screaton">Gavin R. Screaton</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, 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>
</analytic>
<series><title level="j">Nature immunology</title>
<idno type="ISSN">1529-2908</idno>
<idno type="eISSN">1529-2916</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antibodies, Monoclonal (blood)</term>
<term>Antibodies, Monoclonal (isolation & purification)</term>
<term>Antibodies, Monoclonal (metabolism)</term>
<term>Antibodies, Neutralizing (blood)</term>
<term>Antibodies, Neutralizing (isolation & purification)</term>
<term>Biological Assay</term>
<term>Cell Line</term>
<term>Dengue (blood)</term>
<term>Dengue (immunology)</term>
<term>Dengue Virus (immunology)</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Humans</term>
<term>Immunoblotting</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Envelope Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Anticorps monoclonaux (isolement et purification)</term>
<term>Anticorps monoclonaux (métabolisme)</term>
<term>Anticorps monoclonaux (sang)</term>
<term>Anticorps neutralisants (isolement et purification)</term>
<term>Anticorps neutralisants (sang)</term>
<term>Dengue (immunologie)</term>
<term>Dengue (sang)</term>
<term>Dosage biologique</term>
<term>Humains</term>
<term>Immunotransfert</term>
<term>Lignée cellulaire</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Test ELISA</term>
<term>Virus de la dengue (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Antibodies, Neutralizing</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Antibodies, Neutralizing</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Dengue</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Dengue</term>
<term>Protéines de l'enveloppe virale</term>
<term>Virus de la dengue</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Dengue</term>
<term>Dengue Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Anticorps monoclonaux</term>
<term>Anticorps neutralisants</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Anticorps monoclonaux</term>
<term>Protéines de l'enveloppe virale</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps monoclonaux</term>
<term>Anticorps neutralisants</term>
<term>Dengue</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Biological Assay</term>
<term>Cell Line</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Humans</term>
<term>Immunoblotting</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Dosage biologique</term>
<term>Humains</term>
<term>Immunotransfert</term>
<term>Lignée cellulaire</term>
<term>Test ELISA</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en"><p id="P1">Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.</p>
</div>
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