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bioRxiv · 10.1101/2025.08.19.671152

Long Non-Coding RNAs in Response to Ebola Virus Vaccine-Induced Immunity

Mamede, I.·Luscher-Dias, T.·Moscardini, I. F.·Gonzalez, P.·Marinho, B.·Marcon, F.·Hirata, T. D. C.·VSV-EBOPLUS Consortium,·Eichberg, M.·Medaglini, D.·Harandi, A. M.·Siegrist, C. A.·Ottenhoff, T. H. M.·Santoro, F.·Goncalves, A. N. A.·Polidoro, R.·Franco, G. R.·Amaral, P. P.·Nakaya, H.
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Abstract

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their role in shaping human responses to vaccination remains largely uncharacterized. Here, we analyzed RNA-sequencing data from three independent human cohorts vaccinated with the rVSV{Delta}G-ZEBOV-GP Ebola vaccine to profile lncRNA expression dynamics. Using differential expression analysis and correlation meta-analysis across cohorts, we identified an expression signature with several lncRNAs, including LEF1-AS1 and DOCK8-AS1, that exhibit conserved transcriptional activation following vaccination. Correlation of lncRNA expression with gene targets and IgG titers revealed putative roles for lncRNAs in regulating and/or participate in both innate immune responses and adaptive antibody production. Functional enrichment of lncRNA co-expressed protein-coding genes highlighted involvement in T-cell differentiation, interferon signaling, and leukocyte activation. Integrating global run-on sequencing data and comparative transcriptomic analysis across other vaccine studies suggests that LEF1-AS1 modulation is distinctively associated with Ebola vaccination. Our findings demonstrate that lncRNAs are potential integral components of the human vaccine response and provide a foundation for future mechanistic studies targeting noncoding RNA regulation of immunity SignificanceEbola virus remains a significant global health threat due to its high mortality rate and potential for widespread outbreaks, underscoring the urgent need for effective and durable vaccines to control future epidemics. Understanding the transcriptional mechanisms underlying immune responses to vaccination is important to improving vaccine design and efficacy. While protein-coding genes have been extensively studied, the role of long noncoding RNAs (lncRNAs) in vaccine-induced immunity remains poorly understood. Here, we characterize the dynamics of lncRNA expression following administration of the rVSV{Delta}G-ZEBOV-GP Ebola vaccine across multiple human cohorts and identify conserved lncRNA signatures associated with both innate and adaptive immunity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/671152v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@25581aorg.highwire.dtl.DTLVardef@1bb31cforg.highwire.dtl.DTLVardef@c3299eorg.highwire.dtl.DTLVardef@e176b9_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Mamede, I., Luscher-Dias, T., Moscardini, I. F., Gonzalez, P., Marinho, B., Marcon, F., Hirata, T. D. C., VSV-EBOPLUS Consortium,, Eichberg, M., Medaglini, D., Harandi, A. M., Siegrist, C. A., Ottenhoff, T. H. M., Santoro, F., Goncalves, A. N. A., Polidoro, R., Franco, G. R., Amaral, P. P., Nakaya, H.. 2025-08-23. Long Non-Coding RNAs in Response to Ebola Virus Vaccine-Induced Immunity. https://doi.org/10.1101/2025.08.19.671152

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