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

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.

SUBMITTER: Sakabe S

PROVIDER: S-EPMC6094108 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Analysis of CD8<sup>+</sup> T cell response during the 2013-2016 Ebola epidemic in West Africa.

Sakabe Saori S Sullivan Brian M BM Hartnett Jessica N JN Robles-Sikisaka Refugio R Gangavarapu Karthik K Cubitt Beatrice B Ware Brian C BC Kotliar Dylan D Branco Luis M LM Goba Augustine A Momoh Mambu M Sandi John Demby JD Kanneh Lansana L Grant Donald S DS Garry Robert F RF Andersen Kristian G KG de la Torre Juan Carlos JC Sabeti Pardis C PC Schieffelin John S JS Oldstone Michael B A MBA

Proceedings of the National Academy of Sciences of the United States of America 20180723 32

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<sup>+</sup> 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 t ...[more]

PMID: 30038008

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Project description:BackgroundWest African countries Liberia, Sierra Leone, and Guinea experienced the largest and longest epidemic of Ebola virus disease from 2014 to 2016; after the epidemic was declared to be over, Liberia, Guinea, and Sierra Leone still experienced Ebola cases/clusters. The United States Centers for Disease Control and Prevention (US CDC) participated in the response efforts to the latter Ebola clusters, by assisting with case investigation, contact identification, and monitoring. This study aims to estimate the cost to the US CDC of responding to three different Ebola clusters after the end of the Ebola epidemic in 2015: i) Sierra Leone, Tonkolili (Jan 2016, 2 Ebola cases, 5 affected regions); ii) Guinea, Nzerekore (Mar-May 2016, 10 Ebola cases, 2 affected regions); iii) Liberia, Somali Drive (Mar 2016, 3 Ebola cases, 1 affected region).Main textAfter interviewing team members that had participated in the response, we estimated total costs (expressed in 2016 US Dollars [USD]), where total costs correspond to travel costs, deployed personnel costs, costs to prepare for deployment, procurement and interagency collaboration costs, among others. We also estimated cost per cluster case (corresponding to the total costs divided by the total number of cluster cases); and cost per case-affected-region (equal to the total costs divided by the product of the number of cases times the number of regions affected). We found that the response cost varied sixteenfold between USD 113 166 in Liberia and USD 1 764 271 in Guinea, where the main cost drivers were travel and personnel costs. The cost per cluster case varied tenfold between 37 722 in Liberia (three cases) and USD 347 226 in Sierra Leone, and the cost per case-affected-region varied threefold between USD 37 722 in Liberia and USD 88 214 in Guinea.ConclusionsCosts vary with the characteristics of each cluster, with those spanning more regions and cases requiring more resources for case investigation and contact identification and monitoring. These data will assist policy makers plan for similar post-epidemic responses.

Project description:BackgroundAs part of a Phase III trial with the Ebola vaccine rVSVΔG-ZEBOV-GP in Guinea, we invited frontline workers (FLWs) to participate in a sub-study to provide additional information on the immunogenicity of the vaccine.MethodsWe conducted an open-label, non-randomized, single-arm immunogenicity evaluation of one dose of rVSVΔG-ZEBOV-GP among healthy FLWs in Guinea. FLWs who refused vaccination were offered to participate as a control group. We followed participants for 84 days with a subset followed-up for 180 days. The primary endpoint was immune response, as measured by ELISA for ZEBOV-glycoprotein-specific antibodies (ELISA-GP) at 28 days. We also conducted neutralization, whole virion ELISA and enzyme-linked immunospot (ELISPOT) assay for cellular response.ResultsA total of 1172 participants received one dose of vaccine and were followed-up for 84 days, among them 114 participants were followed-up for 180 days. Additionally, 99 participants were included in the control group and followed up for 180 days. Overall, 86.4% (95% CI 84.1-88.4) of vaccinated participants seroresponded at 28 days post-vaccination (ELISA- GP) with 65% of these seroresponding at 14 days post-vaccination. Among those who seroresponded at 28 days, 90.7% (95% CI 82.0-95.4) were still seropositive at 180 days. The proportion of seropositivity in the unvaccinated group was 0.0% (95% CI 0.0-3.8) at 28 days and 5.4% (95% CI 2.1-13.1) at 180 days post-vaccination. We found weak correlation between ELISA-GP and neutralization at baseline but significant pairwise correlation at 28 days post-vaccination. Among samples analysed for cellular response, only 1 (2.2%) exhibited responses towards the Zaire Ebola glycoprotein (Ebola GP ≥ 10) at baseline, 10 (13.5%) at day 28 post-vaccination and 27 (48.2%) at Day 180.ConclusionsWe found one dose of rVSVΔG-ZEBOV-GP to be highly immunogenic at 28- and 180-days post vaccination among frontline workers in Guinea. We also found a cellular response that increased with time.

Dataset Information

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

Publications

Analysis of CD8<sup>+</sup> T cell response during the 2013-2016 Ebola epidemic in West Africa.

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