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

机译:PNAS Plus:2013-2016年西非埃博拉疫情期间CD8 + T细胞反应的分析

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摘要

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.
机译:最近的埃博拉疫情体现了了解和控制新兴感染的重要性。尽管T细胞在急性感染期间清除病毒很重要,但对埃博拉病毒特异性CD8 + T细胞应答的了解却很少。我们调查了2013-2016年在塞拉利昂发生的西非疫情中感染埃博拉病毒(EBOV)的个体的免疫应答,那里> 28,000 EBOV疾病(EVD)病例中大部分发生。我们检查了对8种埃博拉蛋白(GP,sGP,NP,VP24,VP30,VP35和VP40)中的7种的T细胞记忆反应以及相关的幸存者HLA表达。在我们分析的30位受试者中,来自26位幸存者的CD8 + T细胞对至少一种EBOV抗原有反应。在26位应答者中有10位(38%)是少数,对病毒GP或sGP产生CD8 + T细胞应答。相比之下,在26位反应者中,有25位(96%)对病毒NP有反应,对VP24有77%(26个中的20个),对VP​​40有69%(26个中的18个),对VP​​35有42%(26个中的11个),没有回应VP30。向EBOV VP24,VP35和VP40产生CD8 + T细胞的个体也使NPOV产生CD8 + T细胞,但很少产生GP。我们为埃博拉病毒确定了34个CD8 + T细胞表位。我们的数据表明了EBOV NP特异性T细胞应答的免疫优势,并建议将其与EBOV GP一起包含在疫苗中将最好地模拟幸存者应答并在疫苗接种过程中帮助增强细胞介导的免疫力。

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