[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]
Analysis of CD8+ T cell response during the 2013–2016 Ebola epidemic in West Africa
Saori Sakabe, Brian M. Sullivan, Jessica N. Hartnett, Refugio Robles-Sikisaka, Karthik Gangavarapu, Beatrice Cubitt, Brian C. Ware, Dylan Kotliar, Luis M. Branco, Augustine Goba, Mambu Momoh, John Demby Sandi, Lansana Kanneh, Donald S. Grant, Robert F. Garry, Kristian G. Andersen, Juan Carlos de la Torre, Pardis C. Sabeti, John S. Schieffelin, and Michael B. A. Oldstone
PNAS July 23, 2018. 201806200; published ahead of print July 23, 2018. https://doi.org/10.1073/pnas.1806200115
Contributed by Michael B. A. Oldstone, June 18, 2018 (sent for review April 13, 2018; reviewed by Arturo Casadevall and Bruce D. Walker)
Zaire ebolavirus (EBOV) is a viral pathogen of significant global health concern best exemplified by more than 28,000 human infections during the recent West African epidemic. Examining immunity in EBOV disease survivors has been historically difficult due to the occurrence of only small outbreaks in remote regions of central Africa. Consequently, little data exist describing EBOV-specific T cell responses during human infection. We examined virus-specific CD8+ T cell immunity in 32 Sierra Leonean survivors of the 2013–2016 epidemic. CD8+ T cells against the nucleoprotein dominated the EBOV-specific responses in this group, while a minority of individuals harbored memory CD8+ T cells against the EBOV-GP. Our data have implications in designing EBOV vaccines that can elicit cell-mediated immunity in a large group of individuals.
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.
Ebola – virus-specific – CD8 T cells – epitopes – HLA
1 S.S. and B.M.S. contributed equally to this work.
2 To whom correspondence may be addressed. Email: email@example.com or firstname.lastname@example.org.
Author contributions: S.S., B.M.S., R.F.G., K.G.A., J.C.d.l.T., P.C.S., J.S.S., and M.B.A.O. designed research; S.S., B.M.S., J.N.H., R.R.-S., K.G., B.C., B.C.W., D.K., L.M.B., A.G., M.M., J.D.S., L.K., D.S.G., R.F.G., and J.S.S. performed research; S.S., B.M.S., R.R.-S., K.G., D.K., R.F.G., K.G.A., and M.B.A.O. analyzed data; and S.S., B.M.S., and M.B.A.O. wrote the paper.
Reviewers: A.C., The Johns Hopkins Bloomberg School of Public Health; and B.D.W., Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University.
The authors declare no conflict of interest.
Data deposition: The data from this study have been deposited in the Immune Epitope Database, www.iedb.org/SubID/1000771.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1806200115/-/DCSupplemental.
Published under the PNAS license.
Keywords: Ebola; Ebola-Makona; Immunology; Vaccines.