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

Wanwisa Dejnirattisai, Wiyada Wongwiwat, Sunpetchuda Supasa, Xiaokang Zhang, Xinghong Dai, Alexander Rouvinsky, 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 MongkolsapayaGavin Robert Screaton

Research output: Contribution to journalArticleResearchpeer-review

276 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)170-177
Number of pages8
JournalNature Immunology
Volume16
Issue number2
DOIs
Publication statusPublished - 16 Jan 2015
Externally publishedYes

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