Division of Biomedical Sciences, School of Medicine, University of California-Riverside, Riverside, CA, 92521, USA.
Graduate Program in Genetics, Genomics and Bioinformatics, University of California-Riverside, Riverside, CA, 92521, USA.
Sci Rep. 2017 Apr 20;7(1):919. doi: 10.1038/s41598-017-01032-8.
Ebola virus (EBOV) poses a significant threat to human health as highlighted by the recent epidemic in West Africa. Data from animal studies and a ring vaccination clinical trial conducted in Guinea during the recent epidemic demonstrated that a recombinant VSV where G protein is replaced with EBOV GP (rVSV-EBOV) is safe and highly efficacious. We previously established that antibodies are essential for rVSV-EBOV mediated protection against EBOV; however, the mechanisms by which this vaccine induces a humoral response and the role of T-cells in rVSV-EBOV mediated protection remain poorly understood. Since this is the only vaccine platform that has completed Phase III clinical studies, it is imperative to gain a better understanding of its mechanisms of protection. Therefore, we performed a longitudinal gene expression analysis of samples collected from controls and T-cell-depleted macaques after rVSV-EBOV vaccination and EBOV challenge. We show that rVSV-EBOV vaccination induces gene expression changes consistent with anti-viral immunity and B-cell proliferation. We also report a previously unappreciated role for CD8 T-cells in mediating rVSV-EBOV protection. Finally, limited viral transcription in surviving animals may boost protective responses after EBOV challenge by maintaining transcriptional changes. This study presents a novel approach in determining mechanisms of vaccine efficacy.
埃博拉病毒（EBOV）对人类健康构成重大威胁，最近西非的疫情就凸显了这一点。来自动物研究的数据和最近在几内亚进行的环疫苗临床试验表明，用 EBOV GP 替代 G 蛋白的重组水疱性口炎病毒（rVSV-EBOV）是安全且高度有效的。我们之前的研究表明，抗体是 rVSV-EBOV 介导的针对 EBOV 保护所必需的；然而，该疫苗如何诱导体液反应以及 T 细胞在 rVSV-EBOV 介导的保护中的作用仍知之甚少。由于这是唯一完成 III 期临床试验的疫苗平台，因此必须更好地了解其保护机制。因此，我们对 rVSV-EBOV 接种和 EBOV 挑战后从对照组和 T 细胞耗竭的猕猴中收集的样本进行了纵向基因表达分析。我们表明，rVSV-EBOV 接种诱导的基因表达变化与抗病毒免疫和 B 细胞增殖一致。我们还报告了 CD8 T 细胞在介导 rVSV-EBOV 保护中的先前未被认识到的作用。最后，在幸存动物中有限的病毒转录可能通过维持转录变化来增强 EBOV 挑战后的保护反应。本研究提出了一种确定疫苗功效机制的新方法。
