Analysis of CD8⁺ T cell response during the 2013–2016 Ebola epidemic in West Africa

The recent Ebola epidemic exemplified the importance of understanding and controlling emerging infections. Despite the importance of T cells in clearing virus during acute infection, little is known about Ebola-specific CD8⁺ T cell responses. We investigated immune responses of individuals infected...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2018-08, Vol.115 (32), p.E7578-E7586
Hauptverfasser: Sakabe, Saori, Sullivan, Brian M., Hartnett, Jessica N., Robles-Sikisaka, Refugio, Gangavarapu, Karthik, Cubitt, Beatrice, Ware, Brian C., Kotliar, Dylan, Branco, Luis M., Goba, Augustine, Momoh, Mambu, Sandi, John Demby, Kanneh, Lansana, Grant, Donald S., Garry, Robert F., Andersen, Kristian G., de la Torre, Juan Carlos, Sabeti, Pardis C., Schieffelin, John S., Oldstone, Michael B. A.
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container_end_page E7586
container_issue 32
container_start_page E7578
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 115
creator Sakabe, Saori
Sullivan, Brian M.
Hartnett, Jessica N.
Robles-Sikisaka, Refugio
Gangavarapu, Karthik
Cubitt, Beatrice
Ware, Brian C.
Kotliar, Dylan
Branco, Luis M.
Goba, Augustine
Momoh, Mambu
Sandi, John Demby
Kanneh, Lansana
Grant, Donald S.
Garry, Robert F.
Andersen, Kristian G.
de la Torre, Juan Carlos
Sabeti, Pardis C.
Schieffelin, John S.
Oldstone, Michael B. A.
description The recent Ebola epidemic exemplified the importance of understanding and controlling emerging infections. Despite the importance of T cells in clearing virus during acute infection, little is known about Ebola-specific CD8⁺ T cell responses. We investigated immune responses of individuals infected with Ebola virus (EBOV) during the 2013–2016 West Africa epidemic in Sierra Leone, where the majority of the >28,000 EBOV disease (EVD) cases occurred. We examined T cell memory responses to seven of the eight Ebola proteins (GP, sGP, NP, VP24, VP30, VP35, and VP40) and associated HLA expression in survivors. Of the 30 subjects included in our analysis, CD8⁺ T cells from 26 survivors responded to at least one EBOV antigen. A minority, 10 of 26 responders (38%), made CD8⁺ T cell responses to the viral GP or sGP. In contrast, 25 of the 26 responders (96%) made response to viral NP, 77% to VP24 (20 of 26), 69% to VP40 (18 of 26), 42% (11 of 26) to VP35, with no response to VP30. Individuals making CD8⁺ T cells to EBOV VP24, VP35, and VP40 also made CD8⁺ T cells to NP, but rarely to GP. We identified 34 CD8⁺ T cell epitopes for Ebola. Our data indicate the immunodominance of the EBOV NP-specific T cell response and suggest that its inclusion in a vaccine along with the EBOV GP would best mimic survivor responses and help boost cell-mediated immunity during vaccination.
doi_str_mv 10.1073/pnas.1806200115
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We examined T cell memory responses to seven of the eight Ebola proteins (GP, sGP, NP, VP24, VP30, VP35, and VP40) and associated HLA expression in survivors. Of the 30 subjects included in our analysis, CD8⁺ T cells from 26 survivors responded to at least one EBOV antigen. A minority, 10 of 26 responders (38%), made CD8⁺ T cell responses to the viral GP or sGP. In contrast, 25 of the 26 responders (96%) made response to viral NP, 77% to VP24 (20 of 26), 69% to VP40 (18 of 26), 42% (11 of 26) to VP35, with no response to VP30. Individuals making CD8⁺ T cells to EBOV VP24, VP35, and VP40 also made CD8⁺ T cells to NP, but rarely to GP. We identified 34 CD8⁺ T cell epitopes for Ebola. 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A.</creatorcontrib><title>Analysis of CD8⁺ T cell response during the 2013–2016 Ebola epidemic in West Africa</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The recent Ebola epidemic exemplified the importance of understanding and controlling emerging infections. Despite the importance of T cells in clearing virus during acute infection, little is known about Ebola-specific CD8⁺ T cell responses. We investigated immune responses of individuals infected with Ebola virus (EBOV) during the 2013–2016 West Africa epidemic in Sierra Leone, where the majority of the &gt;28,000 EBOV disease (EVD) cases occurred. We examined T cell memory responses to seven of the eight Ebola proteins (GP, sGP, NP, VP24, VP30, VP35, and VP40) and associated HLA expression in survivors. Of the 30 subjects included in our analysis, CD8⁺ T cells from 26 survivors responded to at least one EBOV antigen. A minority, 10 of 26 responders (38%), made CD8⁺ T cell responses to the viral GP or sGP. In contrast, 25 of the 26 responders (96%) made response to viral NP, 77% to VP24 (20 of 26), 69% to VP40 (18 of 26), 42% (11 of 26) to VP35, with no response to VP30. Individuals making CD8⁺ T cells to EBOV VP24, VP35, and VP40 also made CD8⁺ T cells to NP, but rarely to GP. We identified 34 CD8⁺ T cell epitopes for Ebola. 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source Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry
subjects Adolescent
Adult
Antibodies, Viral - blood
Antibodies, Viral - immunology
Antigens, Viral - immunology
Biological Sciences
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell-mediated immunity
Disease control
Ebola virus
Ebolavirus
Ebolavirus - immunology
Epidemics
Epitopes
Epitopes, T-Lymphocyte - immunology
Female
Hemorrhagic Fever, Ebola - blood
Hemorrhagic Fever, Ebola - epidemiology
Hemorrhagic Fever, Ebola - immunology
Hemorrhagic Fever, Ebola - prevention & control
Histocompatibility antigen HLA
HLA Antigens - blood
HLA Antigens - immunology
Humans
Immunity
Immunodominance
Immunological memory
Lymphocytes
Lymphocytes T
Male
Nucleoproteins - immunology
PNAS Plus
Proteins
Sierra Leone
Survivors
T cell receptors
Vaccination
Vaccination - methods
Viral diseases
Viral Proteins - immunology
VP24 protein
VP40 protein
Young Adult
title Analysis of CD8⁺ T cell response during the 2013–2016 Ebola epidemic in West Africa
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