title: A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus.
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.
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.
authors.forename: Wanwisa
authors.initials: W
authors.lastname: Dejnirattisai
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.
authors.forename: Wiyada
authors.initials: W
authors.lastname: Wongwiwat
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.|Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.|Graduate Program in Immunology, Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Sunpetchuda
authors.initials: S
authors.lastname: Supasa
authors.affiliation: Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.|CNRS UMR 3569 Virologie, Paris, France.
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Xinghong
authors.initials: X
authors.lastname: Dai
authors.affiliation: Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.|CNRS UMR 3569 Virologie, Paris, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rouvinski
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.|The Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Amonrat
authors.initials: A
authors.lastname: Jumnainsong
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Edwards
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
authors.forename: Nguyen Than Ha
authors.initials: NTH
authors.lastname: Quyen
authors.affiliation: Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.
authors.forename: Thaneeya
authors.initials: T
authors.lastname: Duangchinda
authors.affiliation: Division of Structural Biology and Oxford Protein Production Facility, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.|Science Division, Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Grimes
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
authors.forename: Wen-Yang
authors.initials: WY
authors.lastname: Tsai
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
authors.forename: Chih-Yun
authors.initials: CY
authors.lastname: Lai
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
authors.forename: Wei-Kung
authors.initials: WK
authors.lastname: Wang
authors.affiliation: Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.|Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.|Department of Microbiology and Immunology, University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
authors.affiliation: Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.|CNRS UMR 3569 Virologie, Paris, France.
authors.forename: Felix A
authors.initials: FA
authors.lastname: Rey
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.|Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Juthathip
authors.initials: J
authors.lastname: Mongkolsapaya
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Screaton
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000097:blood / Q000302:isolation & purification*; D001681:Biological Assay; D002460:Cell Line; D003715:Dengue / Q000097:blood / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D014759:Viral Envelope Proteins; C466981:glycoprotein E, dengue virus type 4