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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.

Original publication

DOI

10.1038/ni.3058

Type

Journal article

Journal

Nat Immunol

Publication Date

02/2015

Volume

16

Pages

170 - 177

Keywords

Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Biological Assay, Cell Line, Dengue, Dengue Virus, Enzyme-Linked Immunosorbent Assay, Humans, Immunoblotting, Viral Envelope Proteins