Vianello Eleonora, Persson Josefine, Andersson Björn, van Veen Suzanne, Dias Thomaz Lüscher, Santoro Francesco, Östensson Malin, Obudulu Ogonna, Agbajogu Christopher, Torkzadeh Sara, Nakaya Helder I, Medaglini Donata, Siegrist Claire-Anne, Ottenhoff Tom H M, Harandi Ali M
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
iScience. 2023 Nov 23;26(12):108574. doi: 10.1016/j.isci.2023.108574. eCollection 2023 Dec 15.
The vectored Ebola vaccine rVSVΔG-ZEBOV-GP elicits protection against Ebola Virus Disease (EVD). In a study of forty-eight healthy adult volunteers who received either the rVSVΔG-ZEBOV-GP vaccine or placebo, we profiled intracellular microRNAs (miRNAs) from whole blood cells (WB) and circulating miRNAs from serum-derived extracellular vesicles (EV) at baseline and longitudinally following vaccination. Further, we identified early miRNA signatures associated with ZEBOV-specific IgG antibody responses at baseline and up to one year post-vaccination, and pinpointed target mRNA transcripts and pathways correlated to miRNAs whose expression was altered after vaccination by using systems biology approaches. Several miRNAs were differentially expressed (DE) and miRNA signatures predicted high or low IgG ZEBOV-specific antibody levels with high classification performance. The top miRNA discriminators were WB-miR-6810, EV-miR-7151-3p, and EV-miR-4426. An eight-miRNA antibody predictive signature was associated with immune-related target mRNAs and pathways. These findings provide valuable insights into early blood biomarkers associated with rVSVΔG-ZEBOV-GP vaccine-induced IgG antibody responses.
载体埃博拉疫苗rVSVΔG-ZEBOV-GP可诱导机体对埃博拉病毒病（EVD）产生保护作用。在一项针对48名健康成年志愿者的研究中，这些志愿者分别接种了rVSVΔG-ZEBOV-GP疫苗或安慰剂，我们在基线期以及接种疫苗后的纵向时间点，对全血细胞（WB）中的细胞内微小RNA（miRNA）和血清来源的细胞外囊泡（EV）中的循环miRNA进行了分析。此外，我们确定了在基线期以及接种疫苗后长达一年的时间里，与ZEBOV特异性IgG抗体反应相关的早期miRNA特征，并通过系统生物学方法，找出了与接种疫苗后表达发生改变的miRNA相关的靶mRNA转录本和信号通路。有几种miRNA存在差异表达（DE），并且miRNA特征能够以较高的分类性能预测高或低的IgG ZEBOV特异性抗体水平。最具鉴别力的miRNA是WB-miR-6810、EV-miR-7151-3p和EV-miR-4426。一个由8种miRNA组成的抗体预测特征与免疫相关的靶mRNA和信号通路相关。这些发现为与rVSVΔG-ZEBOV-GP疫苗诱导的IgG抗体反应相关的早期血液生物标志物提供了有价值的见解。
