Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus

Cell Rep. 2019 Nov 26;29(9):2537-2545.e3. doi: 10.1016/j.celrep.2019.10.105.

Abstract

Ebolavirus causes highly lethal hemorrhagic fever in humans. The envelope-displayed viral glycoprotein (GP) is the primary target of humoral immunity induced by natural exposure and vaccination. No T cell epitopes in the GP have been characterized in humans. A phase I clinical trial of a heterologous prime-boost vaccination regime with viral vectors encoding filovirus antigens elicits humoral and T cell responses in vaccinees. The most frequently recognized peptide pools are deconvoluted to identify the minimal epitopes recognized by antigen-specific T cells. We characterize nine immunogenic epitopes on the Ebolavirus GP. Histocompatibility leukocyte antigen (HLA) typing with in silico epitope analysis determines the likely MHC class I restriction elements. Thirteen HLA-A and -B alleles are predicted to present the identified CD8+ T cell epitopes, suggesting promiscuous recognition and a broad immune response. Delivery of the Ebolavirus GP antigen by using a heterologous prime-boost approach is immunogenic in genetically diverse human populations, with responses against multiple epitopes.

Keywords: CD8 T cells; Ebola; HLA-restriction; epitope-mapping; humans; vaccine.

Publication types

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

MeSH terms

  • Ebolavirus / immunology*
  • Epitopes, T-Lymphocyte / immunology*
  • Glycoproteins / immunology*
  • Histocompatibility Antigens Class I / immunology*
  • Humans

Substances

  • Epitopes, T-Lymphocyte
  • Glycoproteins
  • Histocompatibility Antigens Class I