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 Rouvinski, 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 R Screaton

Research output: Contribution to journalArticlepeer-review

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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 languageAmerican English
Pages (from-to)170-177
Number of pages8
JournalNature Immunology
Issue number2
StatePublished - Feb 2015

Bibliographical note

Funding Information:
We thank the Armed Forces Research Institute of Medical Sciences of Thailand (AFRIMS), C. Puttikhunt (National Center for Genetic Engineering and Biotechnology, Thailand) and W. Kasinrerk (Chiang Mai University) for the mouse mAb 4G2 to DENV E protein and mAb 1H10 to DENV; E. Harris (University of California Berkeley School of Public Health) for mAb E1D8 to DENV NS3 protein; H. Wardemann (Max Planck Institute for Infection Biology) for expression vectors for IgG1 or immunoglobulin κ-chain or λ-chain; A Flanagan (University of Oxford) for recombinant soluble E protein; the staff at Oxford University Clinical Research Unit Viet Nam for sample collection; and N. Ferguson (Imperial College London) for statistical advice. We acknowledge the use of instruments at the Electron Imaging Center for Nanomachines, supported by University of California Los Angeles and the US National Institutes of Health (1S10OD018111 and NSF DBI-1338135). Supported by the Medical Research Council UK, the Wellcome Trust (G.R.S.), the National Institutes for Health Research Biomedical Research Centre, the US National Institutes of Health (GM071940 and AI094386), European Commission Seventh Framework Programme (FP7/2007-2013; DENFREE project, 282 378) and the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (S.S. and J.M.).

Publisher Copyright:
© 2015 Nature America, Inc.


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


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