| Literature DB >> 26138979 |
Guntur Fibriansah1, Kristie D Ibarra2, Thiam-Seng Ng1, Scott A Smith3, Joanne L Tan1, Xin-Ni Lim1, Justin S G Ooi1, Victor A Kostyuchenko1, Jiaqi Wang1, Aravinda M de Silva4, Eva Harris2, James E Crowe5, Shee-Mei Lok6.
Abstract
There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.Entities:
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Year: 2015 PMID： 26138979 PMCID： PMC4672004 DOI： 10.1126/science.aaa8651
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728