Structural highlights
Publication Abstract from PubMed
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.
Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope.,Rouvinski A, Dejnirattisai W, Guardado-Calvo P, Vaney MC, Sharma A, Duquerroy S, Supasa P, Wongwiwat W, Haouz A, Barba-Spaeth G, Mongkolsapaya J, Rey FA, Screaton GR Nat Commun. 2017 May 23;8:15411. doi: 10.1038/ncomms15411. PMID:28534525[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rouvinski A, Dejnirattisai W, Guardado-Calvo P, Vaney MC, Sharma A, Duquerroy S, Supasa P, Wongwiwat W, Haouz A, Barba-Spaeth G, Mongkolsapaya J, Rey FA, Screaton GR. Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope. Nat Commun. 2017 May 23;8:15411. doi: 10.1038/ncomms15411. PMID:28534525 doi:http://dx.doi.org/10.1038/ncomms15411
