Longitudinal Human Antibody Repertoire against Complete Viral Proteome from Ebola Virus Survivor Reveals Protective Sites for Vaccine Design

Cell Host Microbe. 2020 Feb 12;27(2):262-276.e4. doi: 10.1016/j.chom.2020.01.001.


Evolution of antibody repertoire against the Ebola virus (EBOV) proteome was characterized in an acutely infected patient receiving supportive care alone to elucidate virus-host interactions over time. Differential kinetics are observed for IgM-IgG-IgA epitope diversity, antibody binding, and affinity maturation to EBOV proteins. During acute illness, antibodies predominate to VP40 and glycoprotein (GP). At day 13 of clinical illness, a marked increase in antibody titers to most EBOV proteins and affinity maturation to GP is associated with rapid decline in viral replication and illness severity. At one year, despite undetectable virus, a diverse IgM repertoire against VP40 and GP epitopes is observed suggesting occult viral persistence. Rabbit immunization experiments identify key immunodominant sites of GP, while challenge studies in mice found these epitopes induce EBOV-neutralizing antibodies and protect against lethal EBOV challenge. This study reveals markers of viral persistence and provides promising approaches for development and evaluation of vaccines and therapeutics.

Keywords: Ebola; GFPDL; GP; affinity; antibody; correlates of protection; epitope mapping; genome-fragment phage display library; glycoprotein; immune response; infection; neutralization; vaccine; virus.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology*
  • Ebolavirus / immunology*
  • Epitopes / immunology
  • Hemorrhagic Fever, Ebola / immunology*
  • Hemorrhagic Fever, Ebola / prevention & control
  • Hemorrhagic Fever, Ebola / therapy
  • Humans
  • Immunoglobulin A / isolation & purification
  • Immunoglobulin G / isolation & purification
  • Immunoglobulin M / isolation & purification
  • Mice
  • Proteome / immunology
  • Rabbits
  • Survivors
  • Viral Envelope Proteins / immunology
  • Viral Matrix Proteins / immunology
  • Viral Proteins / immunology
  • Viral Vaccines


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Proteome
  • VP40 protein, virus
  • Viral Envelope Proteins
  • Viral Matrix Proteins
  • Viral Proteins
  • Viral Vaccines