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

Author:

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.ORCID,Andersen Kristian G.,de la Torre Juan Carlos,Sabeti Pardis C.,Schieffelin John S.,Oldstone Michael B. A.ORCID

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.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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