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

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 heterologou...

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Autores principales: Powlson, Jonathan, Wright, Daniel, Zeltina, Antra, Giza, Mark, Nielsen, Morten, Rampling, Tommy, Venkatrakaman, Navin, Bowden, Thomas A., Hill, Adrian V.S., Ewer, Katie J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899439/
https://www.ncbi.nlm.nih.gov/pubmed/31775024
http://dx.doi.org/10.1016/j.celrep.2019.10.105
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author Powlson, Jonathan
Wright, Daniel
Zeltina, Antra
Giza, Mark
Nielsen, Morten
Rampling, Tommy
Venkatrakaman, Navin
Bowden, Thomas A.
Hill, Adrian V.S.
Ewer, Katie J.
author_facet Powlson, Jonathan
Wright, Daniel
Zeltina, Antra
Giza, Mark
Nielsen, Morten
Rampling, Tommy
Venkatrakaman, Navin
Bowden, Thomas A.
Hill, Adrian V.S.
Ewer, Katie J.
author_sort Powlson, Jonathan
collection PubMed
description 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.
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spelling pubmed-68994392020-01-21 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. Cell Rep Article 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. Cell Press 2019-11-26 /pmc/articles/PMC6899439/ /pubmed/31775024 http://dx.doi.org/10.1016/j.celrep.2019.10.105 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
title Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus
title_full Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus
title_fullStr Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus
title_full_unstemmed Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus
title_short Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus
title_sort characterization of antigenic mhc-class-i-restricted t cell epitopes in the glycoprotein of ebolavirus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899439/
https://www.ncbi.nlm.nih.gov/pubmed/31775024
http://dx.doi.org/10.1016/j.celrep.2019.10.105
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