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

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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

Cite this

Powlson, Jonathan ; Wright, Daniel ; Zeltina, Antra ; Giza, Mark ; Nielsen, Morten ; Rampling, Tommy ; Venkatrakaman, Navin ; Bowden, Thomas A. ; Hill, Adrian V.S. ; Ewer, Katie J. / Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus. In: Cell Reports. 2019 ; Vol. 29, No. 9. pp. 2537-2545.e3.
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title = "Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus",
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.",
author = "Jonathan Powlson and Daniel Wright and Antra Zeltina and Mark Giza and Morten Nielsen and Tommy Rampling and Navin Venkatrakaman and Bowden, {Thomas A.} and Hill, {Adrian V.S.} and Ewer, {Katie J.}",
year = "2019",
doi = "10.1016/j.celrep.2019.10.105",
language = "English",
volume = "29",
pages = "2537--2545.e3",
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issn = "2211-1247",
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Powlson, J, Wright, D, Zeltina, A, Giza, M, Nielsen, M, Rampling, T, Venkatrakaman, N, Bowden, TA, Hill, AVS & Ewer, KJ 2019, 'Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus', Cell Reports, vol. 29, no. 9, pp. 2537-2545.e3. https://doi.org/10.1016/j.celrep.2019.10.105

Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus. / Powlson, Jonathan; Wright, Daniel; Zeltina, Antra; Giza, Mark; Nielsen, Morten; Rampling, Tommy; Venkatrakaman, Navin; Bowden, Thomas A.; Hill, Adrian V.S.; Ewer, Katie J.

In: Cell Reports, Vol. 29, No. 9, 2019, p. 2537-2545.e3.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus

AU - Powlson, Jonathan

AU - Wright, Daniel

AU - Zeltina, Antra

AU - Giza, Mark

AU - Nielsen, Morten

AU - Rampling, Tommy

AU - Venkatrakaman, Navin

AU - Bowden, Thomas A.

AU - Hill, Adrian V.S.

AU - Ewer, Katie J.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2019.10.105

DO - 10.1016/j.celrep.2019.10.105

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