Global blood miRNA profiling unravels early signatures of immunogenicity of Ebola vaccine rVSV?G-ZEBOV-GP

We characterized the extracellular miRNAs, isolated from serum-derived extracellular vesicles (EV), induced by vaccination against Ebola. We identified early miRNA signatures associated with the ZEBOV-specific IgG antibody responses at day 28 or 360 post-vaccination. Overall design: We isolated total RNA including miRNA from serum-derived extracellular vesicles (EV) from 48 healthy individuals receiving the rVSV?G-ZEBOV-GP vaccine or placebo. Timepoints day 0 (baseline before vaccination), and days 1, 2, 3, 4 and 7 post-vaccination have been considered. We performed miRNA-seq. We then identified differentially expressed miRNAs by comparing rVSV?G-ZEBOV-GP vaccines vs placebo controls. Next, we correlated baseline and early miRNAs with the ZEBOV-specific IgG antibody titer measured at day 28 and day 360 by performing Pearson Correlation. We used Machine Learning algorithms to identify the best early miRNA signatures able to discriminate high and low antibody levels at day 28 and day 360. Finally, we identified a miRNA antibody predictive signature associated with immune-related target mRNAs and corresponding pathways. VEBCON Consortium VSV-EBOVAC Consortium VSV-EBOPLUS Consortium

本研究对埃博拉疫苗诱导、并从血清来源细胞外囊泡（extracellular vesicles, EV）中分离得到的细胞外微RNA（miRNA）进行了系统表征分析，鉴定出了疫苗接种后第28天或第360天与ZEBOV特异性IgG抗体应答相关的早期miRNA特征谱。

实验设计概况：本研究从48名接种rVSVΔG-ZEBOV-GP疫苗或安慰剂的健康受试者中，提取了血清来源细胞外囊泡（EV）内包含miRNA在内的总RNA；采集了接种前第0天（基线）以及接种后第1、2、3、4、7天的样本，并完成了miRNA测序。通过对比rVSVΔG-ZEBOV-GP疫苗组与安慰剂对照组，本研究鉴定出差异表达的miRNA；随后通过皮尔逊相关分析，将基线及早期miRNA与接种后第28天、第360天检测的ZEBOV特异性IgG抗体滴度进行关联分析。本研究采用机器学习算法，筛选出可区分接种后第28天及第360天高、低抗体水平的最优早期miRNA特征谱；最终鉴定出与免疫相关靶标mRNA及对应通路相关的miRNA抗体预测特征谱。

VEBCON联盟、VSV-EBOVAC联盟及VSV-EBOPLUS联盟