Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor-Binding Site

Cell Rep. 2016 May 17;15(7):1514-1526. doi: 10.1016/j.celrep.2016.04.026. Epub 2016 May 5.


Previous efforts to identify cross-neutralizing antibodies to the receptor-binding site (RBS) of ebolavirus glycoproteins have been unsuccessful, largely because the RBS is occluded on the viral surface. We report a monoclonal antibody (FVM04) that targets a uniquely exposed epitope within the RBS; cross-neutralizes Ebola (EBOV), Sudan (SUDV), and, to a lesser extent, Bundibugyo viruses; and shows protection against EBOV and SUDV in mice and guinea pigs. The antibody cocktail ZMapp™ is remarkably effective against EBOV (Zaire) but does not cross-neutralize other ebolaviruses. By replacing one of the ZMapp™ components with FVM04, we retained the anti-EBOV efficacy while extending the breadth of protection to SUDV, thereby generating a cross-protective antibody cocktail. In addition, we report several mutations at the base of the ebolavirus glycoprotein that enhance the binding of FVM04 and other cross-reactive antibodies. These findings have important implications for pan-ebolavirus vaccine development and defining broadly protective antibody cocktails.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal / ultrastructure
  • Antibodies, Neutralizing
  • Antibodies, Viral / chemistry
  • Binding Sites
  • Disease Models, Animal
  • Ebolavirus / physiology*
  • Epitopes / immunology*
  • Female
  • Glycoproteins / chemistry
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Glycoproteins / ultrastructure
  • Guinea Pigs
  • HEK293 Cells
  • Hemorrhagic Fever, Ebola / immunology*
  • Humans
  • Kinetics
  • Mice, Inbred BALB C
  • Models, Molecular
  • Mutation / genetics
  • Negative Staining
  • Neutralization Tests
  • Receptors, Virus / metabolism*
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Glycoproteins
  • Receptors, Virus