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Nat Immunol. 2015 Feb;16(2):170-177. doi: 10.1038/ni.3058. Epub 2014 Dec 15.

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

Author information

1
Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK.
2
Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
3
Graduate Program in Immunology, Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
4
Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.
5
CNRS UMR 3569 Virologie, Paris, France.
6
Department of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.
7
The Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
8
Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
9
Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.
10
Division of Structural Biology and Oxford Protein Production Facility, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
11
Science Division, Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, UK.
12
Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
13
Department of Microbiology and Immunology, University of Melbourne, Carlton, Victoria, Australia.
#
Contributed equally

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.

PMID:
25501631
PMCID:
PMC4445969
DOI:
10.1038/ni.3058
[Indexed for MEDLINE]
Free PMC Article

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