Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection

Cell. 2016 Jan 28;164(3):392-405. doi: 10.1016/j.cell.2015.12.022. Epub 2016 Jan 21.

Abstract

Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / immunology*
  • Cross Reactions
  • Disease Models, Animal
  • Ebolavirus / immunology*
  • Epitope Mapping
  • Guinea Pigs
  • Hemorrhagic Fever, Ebola / immunology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron
  • Models, Molecular
  • Mutagenesis
  • Survivors*
  • Uganda

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing