by Guntur Fibriansah, Kristie D Ibarra, Thiam-Seng Ng, Scott A Smith, Joanne L Tan, Xin-Ni Lim, Justin S G Ooi, Victor A Kostyuchenko, Jiaqi Wang, Aravinda M de Silva, Eva Harris, James E Crowe Jr, Shee-Mei Lok
Science 3 July 2015: Vol. 349 no. 6243 pp. 88-91. DOI: 10.1126/science.aaa8651
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.