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

Jonathan Powlson, Daniel Wright, Antra Zeltina, Mark Giza, Morten Nielsen, Tommy Rampling, Navin Venkatrakaman, Thomas A. Bowden, Adrian V.S. Hill, Katie J. Ewer*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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.
Original languageEnglish
JournalCell Reports
Volume29
Issue number9
Pages (from-to)2537-2545.e3
ISSN2211-1247
DOIs
Publication statusPublished - 2019

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