A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus
Wanwisa Dejnirattisaia, Wiyada Wongwiwata, Sunpetchuda Supasaa b c, Xiaokang Zhangd e f, Xinghong Daig, Alexander Rouvinskid e f, Amonrat Jumnainsonga h, Carolyn Edwardsa, Nguyen Than Ha Quyeni, Thaneeya Duangchindaj, Jonathan M. Grimesk l, Wen-Yang Tsaim, Chih-Yun Laim, Wei‐Kung Wangm, Prida Malasitb j, Jeremy Farrari, Cameron Paul Simmonsi n, Zehua Zhoug, Felix Augusto Reyd e, Juthathip Mongkolsapayaa b✉, Gavin Robert Screatona✉
- aDivision of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, London, UK
- bDengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
- cGraduate Program in Immunology, Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
- dCNRS UMR 3569 Virologie, Paris, France
- eInstitut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France
- fDépartement de Virologie, Institut Pasteur, Unité de Virologie Structurale, Paris, France
- gDepartment of Microbiology, Immunology and Molecular Genetics and California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA
- hThe Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand
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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.
TL;DRThe 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. (Semantic Scholar)