A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus.
Identifieur interne : 003024 ( PubMed/Corpus ); précédent : 003023; suivant : 003025A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus.
Auteurs : Wanwisa Dejnirattisai ; Wiyada Wongwiwat ; Sunpetchuda Supasa ; Xiaokang Zhang ; Xinghong Dai ; Alexander Rouvinski ; Amonrat Jumnainsong ; Carolyn Edwards ; Nguyen Than Ha Quyen ; Thaneeya Duangchinda ; Jonathan M. Grimes ; Wen-Yang Tsai ; Chih-Yun Lai ; Wei-Kung Wang ; Prida Malasit ; Jeremy Farrar ; Cameron P. Simmons ; Z Hong Zhou ; Felix A. Rey ; Juthathip Mongkolsapaya ; Gavin R. ScreatonSource :
- Nature immunology [ 1529-2916 ] ; 2015.
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.
DOI: 10.1038/ni.3058
PubMed: 25501631
Links to Exploration step
pubmed:25501631Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Wongwiwat, Wiyada" sort="Wongwiwat, Wiyada" uniqKey="Wongwiwat W" first="Wiyada" last="Wongwiwat">Wiyada Wongwiwat</name><affiliation><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Supasa, Sunpetchuda" sort="Supasa, Sunpetchuda" uniqKey="Supasa S" first="Sunpetchuda" last="Supasa">Sunpetchuda Supasa</name><affiliation><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Xiaokang" sort="Zhang, Xiaokang" uniqKey="Zhang X" first="Xiaokang" last="Zhang">Xiaokang Zhang</name><affiliation><nlm:affiliation>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Dai, Xinghong" sort="Dai, Xinghong" uniqKey="Dai X" first="Xinghong" last="Dai">Xinghong Dai</name><affiliation><nlm:affiliation>Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rouvinski, Alexander" sort="Rouvinski, Alexander" uniqKey="Rouvinski A" first="Alexander" last="Rouvinski">Alexander Rouvinski</name><affiliation><nlm:affiliation>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Jumnainsong, Amonrat" sort="Jumnainsong, Amonrat" uniqKey="Jumnainsong A" first="Amonrat" last="Jumnainsong">Amonrat Jumnainsong</name><affiliation><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Edwards, Carolyn" sort="Edwards, Carolyn" uniqKey="Edwards C" first="Carolyn" last="Edwards">Carolyn Edwards</name><affiliation><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></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><nlm:affiliation>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:affiliation></affiliation></author><author><name sortKey="Duangchinda, Thaneeya" sort="Duangchinda, Thaneeya" uniqKey="Duangchinda T" first="Thaneeya" last="Duangchinda">Thaneeya Duangchinda</name><affiliation><nlm:affiliation>Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.</nlm:affiliation></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><nlm:affiliation>Division of Structural Biology and Oxford Protein Production Facility, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:affiliation></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><nlm:affiliation>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.</nlm:affiliation></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><nlm:affiliation>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.</nlm:affiliation></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><nlm:affiliation>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Malasit, Prida" sort="Malasit, Prida" uniqKey="Malasit P" first="Prida" last="Malasit">Prida Malasit</name><affiliation><nlm:affiliation>Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.</nlm:affiliation></affiliation></author><author><name sortKey="Farrar, Jeremy" sort="Farrar, Jeremy" uniqKey="Farrar J" first="Jeremy" last="Farrar">Jeremy Farrar</name><affiliation><nlm:affiliation>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:affiliation></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><nlm:affiliation>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:affiliation></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><nlm:affiliation>Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.</nlm:affiliation></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><nlm:affiliation>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mongkolsapaya, Juthathip" sort="Mongkolsapaya, Juthathip" uniqKey="Mongkolsapaya J" first="Juthathip" last="Mongkolsapaya">Juthathip Mongkolsapaya</name><affiliation><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></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><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25501631</idno><idno type="pmid">25501631</idno><idno type="doi">10.1038/ni.3058</idno><idno type="wicri:Area/PubMed/Corpus">003024</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003024</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">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><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Wongwiwat, Wiyada" sort="Wongwiwat, Wiyada" uniqKey="Wongwiwat W" first="Wiyada" last="Wongwiwat">Wiyada Wongwiwat</name><affiliation><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Supasa, Sunpetchuda" sort="Supasa, Sunpetchuda" uniqKey="Supasa S" first="Sunpetchuda" last="Supasa">Sunpetchuda Supasa</name><affiliation><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Xiaokang" sort="Zhang, Xiaokang" uniqKey="Zhang X" first="Xiaokang" last="Zhang">Xiaokang Zhang</name><affiliation><nlm:affiliation>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Dai, Xinghong" sort="Dai, Xinghong" uniqKey="Dai X" first="Xinghong" last="Dai">Xinghong Dai</name><affiliation><nlm:affiliation>Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rouvinski, Alexander" sort="Rouvinski, Alexander" uniqKey="Rouvinski A" first="Alexander" last="Rouvinski">Alexander Rouvinski</name><affiliation><nlm:affiliation>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Jumnainsong, Amonrat" sort="Jumnainsong, Amonrat" uniqKey="Jumnainsong A" first="Amonrat" last="Jumnainsong">Amonrat Jumnainsong</name><affiliation><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Edwards, Carolyn" sort="Edwards, Carolyn" uniqKey="Edwards C" first="Carolyn" last="Edwards">Carolyn Edwards</name><affiliation><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></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><nlm:affiliation>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:affiliation></affiliation></author><author><name sortKey="Duangchinda, Thaneeya" sort="Duangchinda, Thaneeya" uniqKey="Duangchinda T" first="Thaneeya" last="Duangchinda">Thaneeya Duangchinda</name><affiliation><nlm:affiliation>Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.</nlm:affiliation></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><nlm:affiliation>Division of Structural Biology and Oxford Protein Production Facility, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:affiliation></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><nlm:affiliation>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.</nlm:affiliation></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><nlm:affiliation>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.</nlm:affiliation></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><nlm:affiliation>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Malasit, Prida" sort="Malasit, Prida" uniqKey="Malasit P" first="Prida" last="Malasit">Prida Malasit</name><affiliation><nlm:affiliation>Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.</nlm:affiliation></affiliation></author><author><name sortKey="Farrar, Jeremy" sort="Farrar, Jeremy" uniqKey="Farrar J" first="Jeremy" last="Farrar">Jeremy Farrar</name><affiliation><nlm:affiliation>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:affiliation></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><nlm:affiliation>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:affiliation></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><nlm:affiliation>Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.</nlm:affiliation></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><nlm:affiliation>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mongkolsapaya, Juthathip" sort="Mongkolsapaya, Juthathip" uniqKey="Mongkolsapaya J" first="Juthathip" last="Mongkolsapaya">Juthathip Mongkolsapaya</name><affiliation><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></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><nlm:affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Nature immunology</title><idno type="eISSN">1529-2916</idno><imprint><date when="2015" type="published">2015</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="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="immunology" xml:lang="en"><term>Dengue</term><term>Dengue Virus</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></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25501631</PMID><DateCreated><Year>2015</Year><Month>01</Month><Day>17</Day></DateCreated><DateCompleted><Year>2015</Year><Month>04</Month><Day>08</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1529-2916</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>2</Issue><PubDate><Year>2015</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Nature immunology</Title><ISOAbbreviation>Nat. Immunol.</ISOAbbreviation></Journal><ArticleTitle>A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus.</ArticleTitle><Pagination><MedlinePgn>170-177</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/ni.3058</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Dejnirattisai</LastName><ForeName>Wanwisa</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Wongwiwat</LastName><ForeName>Wiyada</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Supasa</LastName><ForeName>Sunpetchuda</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Graduate Program in Immunology, Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaokang</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CNRS UMR 3569 Virologie, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dai</LastName><ForeName>Xinghong</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rouvinski</LastName><ForeName>Alexander</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CNRS UMR 3569 Virologie, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jumnainsong</LastName><ForeName>Amonrat</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Edwards</LastName><ForeName>Carolyn</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Quyen</LastName><ForeName>Nguyen Than Ha</ForeName><Initials>NTH</Initials><AffiliationInfo><Affiliation>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Duangchinda</LastName><ForeName>Thaneeya</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grimes</LastName><ForeName>Jonathan M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Division of Structural Biology and Oxford Protein Production Facility, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Science Division, Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tsai</LastName><ForeName>Wen-Yang</ForeName><Initials>WY</Initials><AffiliationInfo><Affiliation>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lai</LastName><ForeName>Chih-Yun</ForeName><Initials>CY</Initials><AffiliationInfo><Affiliation>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Wei-Kung</ForeName><Initials>WK</Initials><AffiliationInfo><Affiliation>Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Malasit</LastName><ForeName>Prida</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Farrar</LastName><ForeName>Jeremy</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Simmons</LastName><ForeName>Cameron P</ForeName><Initials>CP</Initials><AffiliationInfo><Affiliation>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, Carlton, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Z Hong</ForeName><Initials>ZH</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rey</LastName><ForeName>Felix A</ForeName><Initials>FA</Initials><AffiliationInfo><Affiliation>Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CNRS UMR 3569 Virologie, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mongkolsapaya</LastName><ForeName>Juthathip</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Screaton</LastName><ForeName>Gavin R</ForeName><Initials>GR</Initials><AffiliationInfo><Affiliation>Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>1S10OD018111</GrantID><Acronym>OD</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>095541</GrantID><Agency>Wellcome Trust</Agency><Country>United Kingdom</Country></Grant><Grant><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>R01 AI094386</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>GM071940</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>089276</GrantID><Agency>Wellcome Trust</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>S10 OD018111</GrantID><Acronym>OD</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>G0801508</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>G0600000</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>R01 GM071940</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AI094386</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>G0400720</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>S10 RR023057</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><Agency>Wellcome Trust</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>12</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Nat Immunol</MedlineTA><NlmUniqueID>100941354</NlmUniqueID><ISSNLinking>1529-2908</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000911">Antibodies, Monoclonal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D057134">Antibodies, Neutralizing</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014759">Viral Envelope Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C466981">glycoprotein E, dengue virus type 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MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000302" MajorTopicYN="Y">isolation & purification</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001681" MajorTopicYN="N">Biological Assay</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003715" MajorTopicYN="N">Dengue</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003716" MajorTopicYN="N">Dengue Virus</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004797" MajorTopicYN="N">Enzyme-Linked Immunosorbent Assay</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName 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