Alexander RouvinskiWanwisa DejnirattisaiPablo Guardado-CalvoMarie Christine VaneyArvind SharmaStéphane DuquerroyPiyada SupasaWiyada WongwiwatAhmed HaouzGiovanna Barba-SpaethJuthathip MongkolsapayaFélix A. ReyGavin R. ScreatonInstitut Pasteur, ParisCNRS Centre National de la Recherche ScientifiqueHammersmith HospitalUniversite Paris-Sud XIMahidol UniversityHebrew University-Hadassah Medical School2018-12-212019-03-142018-12-212019-03-142017-05-23Nature Communications. Vol.8, (2017)204117232-s2.0-85019563410https://repository.li.mahidol.ac.th/handle/20.500.14594/41884© 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryArticleSCOPUS10.1038/ncomms15411