Publication: Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope
Issued Date
2017-05-23
Resource Type
ISSN
20411723
Other identifier(s)
2-s2.0-85019563410
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications. Vol.8, (2017)
Suggested Citation
Alexander Rouvinski, Wanwisa Dejnirattisai, Pablo Guardado-Calvo, Marie Christine Vaney, Arvind Sharma, Stéphane Duquerroy, Piyada Supasa, Wiyada Wongwiwat, Ahmed Haouz, Giovanna Barba-Spaeth, Juthathip Mongkolsapaya, Félix A. Rey, Gavin R. Screaton Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope. Nature Communications. Vol.8, (2017). doi:10.1038/ncomms15411 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41884
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope
Abstract
© The Author(s) 2017. A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic 'breathing' of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing. We here engineer E dimers locked by inter-subunit disulfide bonds, and show by X-ray crystallography and by binding to a panel of human antibodies that these engineered dimers do not expose the FLE, while retaining the EDE exposure. These locked dimers are strong immunogen candidates for a next-generation vaccine.