DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers

Science. 2015 Jul 3;349(6243):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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / ultrastructure*
  • Antibodies, Neutralizing / ultrastructure*
  • Coinfection / immunology
  • Cross Reactions
  • Cryoelectron Microscopy
  • Dengue Virus / immunology*
  • Disease Models, Animal
  • Epitopes / immunology
  • Humans
  • Mice
  • Serogroup
  • Viral Envelope Proteins / immunology*


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • Viral Envelope Proteins

Associated data

  • PDB/4UIF
  • PDB/4UIH
  • PDB/5A1Z