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 |
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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. |
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A.</creator><creatorcontrib>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.</creatorcontrib><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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1806200115</identifier><identifier>PMID: 30038008</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>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</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2018-08, Vol.115 (32), p.E7578-E7586</ispartof><rights>Volumes 1–89 and 106–115, copyright as a collective work only; author(s) retains copyright to individual articles</rights><rights>Copyright National Academy of Sciences Aug 7, 2018</rights><rights>2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-22622f57b69c727bcbdbba5bdd979848704956cd39447b563039469fff62c703</citedby><cites>FETCH-LOGICAL-c443t-22622f57b69c727bcbdbba5bdd979848704956cd39447b563039469fff62c703</cites><orcidid>0000-0003-0804-0501 ; 0000-0002-5683-3250</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26530107$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26530107$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30038008$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakabe, Saori</creatorcontrib><creatorcontrib>Sullivan, Brian M.</creatorcontrib><creatorcontrib>Hartnett, Jessica N.</creatorcontrib><creatorcontrib>Robles-Sikisaka, Refugio</creatorcontrib><creatorcontrib>Gangavarapu, Karthik</creatorcontrib><creatorcontrib>Cubitt, Beatrice</creatorcontrib><creatorcontrib>Ware, Brian C.</creatorcontrib><creatorcontrib>Kotliar, Dylan</creatorcontrib><creatorcontrib>Branco, Luis M.</creatorcontrib><creatorcontrib>Goba, Augustine</creatorcontrib><creatorcontrib>Momoh, Mambu</creatorcontrib><creatorcontrib>Sandi, John Demby</creatorcontrib><creatorcontrib>Kanneh, Lansana</creatorcontrib><creatorcontrib>Grant, Donald S.</creatorcontrib><creatorcontrib>Garry, Robert F.</creatorcontrib><creatorcontrib>Andersen, Kristian G.</creatorcontrib><creatorcontrib>de la Torre, Juan Carlos</creatorcontrib><creatorcontrib>Sabeti, Pardis C.</creatorcontrib><creatorcontrib>Schieffelin, John S.</creatorcontrib><creatorcontrib>Oldstone, Michael B. 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 >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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antibodies, Viral - blood</subject><subject>Antibodies, Viral - immunology</subject><subject>Antigens, Viral - immunology</subject><subject>Biological Sciences</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell-mediated immunity</subject><subject>Disease control</subject><subject>Ebola virus</subject><subject>Ebolavirus</subject><subject>Ebolavirus - immunology</subject><subject>Epidemics</subject><subject>Epitopes</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Female</subject><subject>Hemorrhagic Fever, Ebola - blood</subject><subject>Hemorrhagic Fever, Ebola - epidemiology</subject><subject>Hemorrhagic Fever, Ebola - immunology</subject><subject>Hemorrhagic Fever, Ebola - prevention & control</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA Antigens - blood</subject><subject>HLA Antigens - immunology</subject><subject>Humans</subject><subject>Immunity</subject><subject>Immunodominance</subject><subject>Immunological memory</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Nucleoproteins - immunology</subject><subject>PNAS Plus</subject><subject>Proteins</subject><subject>Sierra Leone</subject><subject>Survivors</subject><subject>T cell receptors</subject><subject>Vaccination</subject><subject>Vaccination - methods</subject><subject>Viral diseases</subject><subject>Viral Proteins - immunology</subject><subject>VP24 protein</subject><subject>VP40 protein</subject><subject>Young Adult</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc9u1DAQxi1ERZfCmRPIEhcuacf_4wvSailQqRKXlXq0HMdpvcrGwU4q9QbPwNvwOH0SvNqypZxmpPnNp_nmQ-gNgVMCip2Ng82npAZJAQgRz9CCgCaV5BqeowUAVVXNKT9GL3PeAIAWNbxAxwyA1QD1Al0tB9vf5ZBx7PDqU33_8zdeY-f7Hiefxzhkj9s5heEaTzceUyDs_sevUiQ-b2JvsR9D67fB4TDgK58nvOxScPYVOupsn_3rh3qC1p_P16uv1eW3Lxer5WXlOGdTRamktBOqkdopqhrXtE1jRdO2Wuma1wq4FtK1THOuGiEZlE7qruskdQrYCfq4lx3nZutb54cp2d6MKWxtujPRBvN0MoQbcx1vjQTNCdRF4MODQIrf53K_2Ya8s28HH-dsKCghuGCEFfT9f-gmzqm8r1CEAGVABS3U2Z5yKeacfHc4hoDZZWZ2mZnHzMrGu389HPi_IRXg7R7Y5Cmmw5xKwWCn-AeIW5r4</recordid><startdate>20180807</startdate><enddate>20180807</enddate><creator>Sakabe, Saori</creator><creator>Sullivan, Brian M.</creator><creator>Hartnett, Jessica N.</creator><creator>Robles-Sikisaka, Refugio</creator><creator>Gangavarapu, Karthik</creator><creator>Cubitt, Beatrice</creator><creator>Ware, Brian C.</creator><creator>Kotliar, Dylan</creator><creator>Branco, Luis M.</creator><creator>Goba, Augustine</creator><creator>Momoh, Mambu</creator><creator>Sandi, John Demby</creator><creator>Kanneh, Lansana</creator><creator>Grant, Donald S.</creator><creator>Garry, Robert F.</creator><creator>Andersen, Kristian G.</creator><creator>de la Torre, Juan Carlos</creator><creator>Sabeti, Pardis C.</creator><creator>Schieffelin, John S.</creator><creator>Oldstone, Michael B. 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A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of CD8⁺ T cell response during the 2013–2016 Ebola epidemic in West Africa</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2018-08-07</date><risdate>2018</risdate><volume>115</volume><issue>32</issue><spage>E7578</spage><epage>E7586</epage><pages>E7578-E7586</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>30038008</pmid><doi>10.1073/pnas.1806200115</doi><orcidid>https://orcid.org/0000-0003-0804-0501</orcidid><orcidid>https://orcid.org/0000-0002-5683-3250</orcidid><oa>free_for_read</oa></addata></record> |
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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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