Imperial College London; Mahidol University; Mahidol University; Le Reseau International des Instituts Pasteur (RIIP); Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); UDICE-French Research Universities; Universite Paris Cite; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Khon Kaen University; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); University of Oxford; Wellcome Centre for Human Genetics; University of Oxford; Wellcome Centre for Human Genetics; Diamond Light Source; University of Hawaii System; University of Hawaii Manoa; University of Melbourne
Type
Article
Source Title
NATURE IMMUNOLOGY
Year
2015
Volume
16
Issue
2
Page
170-+
Open Access
Green Accepted, Green Published
Publisher
NATURE PUBLISHING GROUP
DOI
10.1038/ni.3058
Format
PDF
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.
University of California Los Angeles; US National Institutes of Health [1S10OD018111, NSF DBI-1338135, GM071940, AI094386]; Medical Research Council UK; Wellcome Trust; National Institutes for Health Research Biomedical Research Centre; European Commission Seventh Framework Programme (FP7; DENFREE project) [282 378]; MRC [G0400720, G0801508] Funding Source: UKRI; Medical Research Council [G0400720, G0801508] Funding Source: researchfish; National Institute for Health Research [NF-SI-0507-10303] Funding Source: researchfish; NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR023057] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI094386] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM071940] Funding Source: NIH RePORTER; OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD018111] Funding Source: NIH RePORTER; Direct For Biological Sciences [1338135] Funding Source: National Science Foundation
