Structural Basis for a Convergent Immune Response against Ebola Virus

Cell Host Microbe. 2020 Mar 11;27(3):418-427.e4. doi: 10.1016/j.chom.2020.01.007. Epub 2020 Feb 13.


Ebola virus disease is a severe health problem in Africa. Vaccines that display the Zaire ebolavirus glycoprotein spike complex are a prime component for the effort to combat it. The VH3-15/Vλ1-40-based class of antibodies was recently discovered to be a common response in individuals who received the Ebola virus vaccines. These antibodies display attractive properties, and thus likely contribute to the efficacy of the vaccines. Here, we use cryo-EM to elucidate how three VH3-15/Vλ1-40 antibodies from different individuals target the virus and found a convergent mechanism against a partially conserved site on the spike complex. Our study rationalizes the selection of the VH3-15/Vλ1-40 germline genes for specifically targeting this site and highlights Ebolavirus species-specific sequence divergences that may restrict breadth of VH3-15/Vλ1-40-based humoral response. The results from this study could help develop improved immunization schemes and further enable the design of immunogens that would be efficacious against a broader set of Ebolavirus species.

Keywords: Ebola virus; antibodies; electron microscopy; immune response; protein structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Antibody Specificity
  • Cryoelectron Microscopy
  • Ebola Vaccines
  • Ebolavirus
  • Epitopes / immunology
  • HEK293 Cells
  • Humans
  • Protein Binding
  • Protein Structure, Tertiary
  • Viral Envelope Proteins / immunology*


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Ebola Vaccines
  • Epitopes
  • Viral Envelope Proteins
  • envelope glycoprotein, Ebola virus