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A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus

Identifieur interne : 001771 ( Pmc/Checkpoint ); précédent : 001770; suivant : 001772

A 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 :

RBID : PMC:4445969

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


Affiliations:


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PMC:4445969

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<name sortKey="Mongkolsapaya, Juthathip" sort="Mongkolsapaya, Juthathip" uniqKey="Mongkolsapaya J" first="Juthathip" last="Mongkolsapaya">Juthathip Mongkolsapaya</name>
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<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>
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<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>
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<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>
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</profileDesc>
</teiHeader>
<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>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">100941354</journal-id>
<journal-id journal-id-type="pubmed-jr-id">21750</journal-id>
<journal-id journal-id-type="nlm-ta">Nat Immunol</journal-id>
<journal-id journal-id-type="iso-abbrev">Nat. Immunol.</journal-id>
<journal-title-group>
<journal-title>Nature immunology</journal-title>
</journal-title-group>
<issn pub-type="ppub">1529-2908</issn>
<issn pub-type="epub">1529-2916</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">25501631</article-id>
<article-id pub-id-type="pmc">4445969</article-id>
<article-id pub-id-type="doi">10.1038/ni.3058</article-id>
<article-id pub-id-type="manuscript">NIHMS692004</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Dejnirattisai</surname>
<given-names>Wanwisa</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Wongwiwat</surname>
<given-names>Wiyada</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Supasa</surname>
<given-names>Sunpetchuda</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhang</surname>
<given-names>Xiaokang</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Dai</surname>
<given-names>Xinghong</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rouvinski</surname>
<given-names>Alexander</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jumnainsong</surname>
<given-names>Amonrat</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Edwards</surname>
<given-names>Carolyn</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Quyen</surname>
<given-names>Nguyen Than Ha</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Duangchinda</surname>
<given-names>Thaneeya</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Grimes</surname>
<given-names>Jonathan M</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tsai</surname>
<given-names>Wen-Yang</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lai</surname>
<given-names>Chih-Yun</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Wei-Kung</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Malasit</surname>
<given-names>Prida</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Farrar</surname>
<given-names>Jeremy</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Simmons</surname>
<given-names>Cameron P</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhou</surname>
<given-names>Z Hong</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rey</surname>
<given-names>Felix A</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mongkolsapaya</surname>
<given-names>Juthathip</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Screaton</surname>
<given-names>Gavin R</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK</aff>
<aff id="A2">
<label>2</label>
Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand</aff>
<aff id="A3">
<label>3</label>
Graduate Program in Immunology, Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand</aff>
<aff id="A4">
<label>4</label>
Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France</aff>
<aff id="A5">
<label>5</label>
CNRS UMR 3569 Virologie, Paris, France</aff>
<aff id="A6">
<label>6</label>
Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA</aff>
<aff id="A7">
<label>7</label>
The Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand</aff>
<aff id="A8">
<label>8</label>
Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam</aff>
<aff id="A9">
<label>9</label>
Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand</aff>
<aff id="A10">
<label>10</label>
Division of Structural Biology and Oxford Protein Production Facility, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</aff>
<aff id="A11">
<label>11</label>
Science Division, Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, UK</aff>
<aff id="A12">
<label>12</label>
Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA</aff>
<aff id="A13">
<label>13</label>
Department of Microbiology and Immunology, University of Melbourne, Carlton, Victoria, Australia</aff>
<author-notes>
<corresp id="CR1">Correspondence should be addressed to G.R.S. (
<email>g.screaton@imperial.ac.uk</email>
) or J.M. (
<email>j.mongkolsapaya@imperial.ac.uk</email>
).</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>20</day>
<month>5</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub">
<day>15</day>
<month>12</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub">
<month>2</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>01</day>
<month>8</month>
<year>2015</year>
</pub-date>
<volume>16</volume>
<issue>2</issue>
<fpage>170</fpage>
<lpage>177</lpage>
<pmc-comment>elocation-id from pubmed: 10.1038/ni.3058</pmc-comment>
<permissions>
<copyright-statement>© 2015 Nature America, Inc. All rights reserved.</copyright-statement>
<copyright-year>2015</copyright-year>
<license license-type="permissions-link">
<license-p>Reprints and permissions information is available online at
<ext-link ext-link-type="uri" xlink:href="http://www.nature.com/reprints/index.html">http://www.nature.com/reprints/index.html</ext-link>
.</license-p>
</license>
</permissions>
<abstract>
<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>
</abstract>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>France</li>
<li>Royaume-Uni</li>
<li>Thaïlande</li>
<li>Viêt Nam</li>
<li>États-Unis</li>
</country>
<region>
<li>Angleterre</li>
<li>Californie</li>
<li>Grand Londres</li>
<li>Hawaï</li>
<li>Oxfordshire</li>
<li>Victoria (État)</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Londres</li>
<li>Melbourne</li>
<li>Oxford</li>
<li>Paris</li>
</settlement>
<orgName>
<li>Université d'Oxford</li>
<li>Université de Melbourne</li>
</orgName>
</list>
<tree>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Dejnirattisai, Wanwisa" sort="Dejnirattisai, Wanwisa" uniqKey="Dejnirattisai W" first="Wanwisa" last="Dejnirattisai">Wanwisa Dejnirattisai</name>
</region>
<name sortKey="Edwards, Carolyn" sort="Edwards, Carolyn" uniqKey="Edwards C" first="Carolyn" last="Edwards">Carolyn Edwards</name>
<name sortKey="Grimes, Jonathan M" sort="Grimes, Jonathan M" uniqKey="Grimes J" first="Jonathan M" last="Grimes">Jonathan M. Grimes</name>
<name sortKey="Grimes, Jonathan M" sort="Grimes, Jonathan M" uniqKey="Grimes J" first="Jonathan M" last="Grimes">Jonathan M. Grimes</name>
<name sortKey="Jumnainsong, Amonrat" sort="Jumnainsong, Amonrat" uniqKey="Jumnainsong A" first="Amonrat" last="Jumnainsong">Amonrat Jumnainsong</name>
<name sortKey="Mongkolsapaya, Juthathip" sort="Mongkolsapaya, Juthathip" uniqKey="Mongkolsapaya J" first="Juthathip" last="Mongkolsapaya">Juthathip Mongkolsapaya</name>
<name sortKey="Screaton, Gavin R" sort="Screaton, Gavin R" uniqKey="Screaton G" first="Gavin R" last="Screaton">Gavin R. Screaton</name>
<name sortKey="Supasa, Sunpetchuda" sort="Supasa, Sunpetchuda" uniqKey="Supasa S" first="Sunpetchuda" last="Supasa">Sunpetchuda Supasa</name>
<name sortKey="Wongwiwat, Wiyada" sort="Wongwiwat, Wiyada" uniqKey="Wongwiwat W" first="Wiyada" last="Wongwiwat">Wiyada Wongwiwat</name>
</country>
<country name="Thaïlande">
<noRegion>
<name sortKey="Supasa, Sunpetchuda" sort="Supasa, Sunpetchuda" uniqKey="Supasa S" first="Sunpetchuda" last="Supasa">Sunpetchuda Supasa</name>
</noRegion>
<name sortKey="Duangchinda, Thaneeya" sort="Duangchinda, Thaneeya" uniqKey="Duangchinda T" first="Thaneeya" last="Duangchinda">Thaneeya Duangchinda</name>
<name sortKey="Jumnainsong, Amonrat" sort="Jumnainsong, Amonrat" uniqKey="Jumnainsong A" first="Amonrat" last="Jumnainsong">Amonrat Jumnainsong</name>
<name sortKey="Malasit, Prida" sort="Malasit, Prida" uniqKey="Malasit P" first="Prida" last="Malasit">Prida Malasit</name>
<name sortKey="Malasit, Prida" sort="Malasit, Prida" uniqKey="Malasit P" first="Prida" last="Malasit">Prida Malasit</name>
<name sortKey="Mongkolsapaya, Juthathip" sort="Mongkolsapaya, Juthathip" uniqKey="Mongkolsapaya J" first="Juthathip" last="Mongkolsapaya">Juthathip Mongkolsapaya</name>
<name sortKey="Supasa, Sunpetchuda" sort="Supasa, Sunpetchuda" uniqKey="Supasa S" first="Sunpetchuda" last="Supasa">Sunpetchuda Supasa</name>
</country>
<country name="France">
<region name="Île-de-France">
<name sortKey="Zhang, Xiaokang" sort="Zhang, Xiaokang" uniqKey="Zhang X" first="Xiaokang" last="Zhang">Xiaokang Zhang</name>
</region>
<name sortKey="Rey, Felix A" sort="Rey, Felix A" uniqKey="Rey F" first="Felix A" last="Rey">Felix A. Rey</name>
<name sortKey="Rey, Felix A" sort="Rey, Felix A" uniqKey="Rey F" first="Felix A" last="Rey">Felix A. Rey</name>
<name sortKey="Rouvinski, Alexander" sort="Rouvinski, Alexander" uniqKey="Rouvinski A" first="Alexander" last="Rouvinski">Alexander Rouvinski</name>
<name sortKey="Rouvinski, Alexander" sort="Rouvinski, Alexander" uniqKey="Rouvinski A" first="Alexander" last="Rouvinski">Alexander Rouvinski</name>
<name sortKey="Zhang, Xiaokang" sort="Zhang, Xiaokang" uniqKey="Zhang X" first="Xiaokang" last="Zhang">Xiaokang Zhang</name>
</country>
<country name="États-Unis">
<region name="Californie">
<name sortKey="Dai, Xinghong" sort="Dai, Xinghong" uniqKey="Dai X" first="Xinghong" last="Dai">Xinghong Dai</name>
</region>
<name sortKey="Lai, Chih Yun" sort="Lai, Chih Yun" uniqKey="Lai C" first="Chih-Yun" last="Lai">Chih-Yun Lai</name>
<name sortKey="Tsai, Wen Yang" sort="Tsai, Wen Yang" uniqKey="Tsai W" first="Wen-Yang" last="Tsai">Wen-Yang Tsai</name>
<name sortKey="Wang, Wei Kung" sort="Wang, Wei Kung" uniqKey="Wang W" first="Wei-Kung" last="Wang">Wei-Kung Wang</name>
<name sortKey="Zhou, Z Hong" sort="Zhou, Z Hong" uniqKey="Zhou Z" first="Z Hong" last="Zhou">Z Hong Zhou</name>
</country>
<country name="Viêt Nam">
<noRegion>
<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>
</noRegion>
<name sortKey="Farrar, Jeremy" sort="Farrar, Jeremy" uniqKey="Farrar J" first="Jeremy" last="Farrar">Jeremy Farrar</name>
<name sortKey="Simmons, Cameron P" sort="Simmons, Cameron P" uniqKey="Simmons C" first="Cameron P" last="Simmons">Cameron P. Simmons</name>
</country>
<country name="Australie">
<region name="Victoria (État)">
<name sortKey="Simmons, Cameron P" sort="Simmons, Cameron P" uniqKey="Simmons C" first="Cameron P" last="Simmons">Cameron P. Simmons</name>
</region>
</country>
</tree>
</affiliations>
</record>

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