# Long non-coding RNAs in response to Ebola virus vaccine-induced immunity

**Authors:** Izabela Mamede, Thomaz Luschër-Dias, Isabelle Franco Moscardini, Patrícia Gonzales-Dias, Bárbara Marinho, Fernando Marcon, Thiago Dominguez Crespo Hirata, Michael Eichberg, Donata Medaglini, Ali M. Harandi, Claire-Anne Siegrist, Tom H. M. Ottenhoff, Francesco Santoro, Marylyn M. Addo, André Gonçalves, Daniela M. Ferreira, Rafael Polidoro, Glória R. Franco, Paulo P. Amaral, Helder Nakaya

PMC · DOI: 10.3389/fimmu.2025.1695514 · Frontiers in Immunology · 2026-02-10

## TL;DR

This study explores how long non-coding RNAs respond to an Ebola vaccine, revealing their potential role in immune responses and antibody production.

## Contribution

The study identifies conserved lncRNA expression signatures and their potential roles in immune responses following Ebola vaccination.

## Key findings

- lncRNAs like LEF1-AS1 and DOCK8-AS1 show conserved activation after vaccination.
- lncRNA expression correlates with immune gene activity and antibody levels.
- LEF1-AS1 is uniquely associated with the Ebola vaccine response.

## 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 rVSVΔG-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.

Timeline and analysis of EBOLA vaccine response integrated in the analyses. It includes four vaccine groups (VSV-EBOVAC B1, VSV-EBOVAC B2, EBOPLUS and VEBCON) and sample sizes (n = 46, n = 52, n = 33, n = 18). RNA sequencing and IgG titer measurement processes are illustrated. Key figures show analyses that were perfomed: differential expression of lncRNAs and correlations between lncRNA, mRNA, and IgG titers, highlighting changes post-vaccination, including specific lncRNAs like DOCK8-AS1. Data is presented with graphs and correlation plots.

## Linked entities

- **Genes:** LEF1-AS1 (LEF1 antisense RNA 1) [NCBI Gene 641518], DOCK8-AS1 (DOCK8 antisense RNA 1) [NCBI Gene 157983]
- **Diseases:** Ebola (MONDO:0005737)

## Full-text entities

- **Genes:** CXCL2 (C-X-C motif chemokine ligand 2) [NCBI Gene 2920] {aka CINC-2a, GRO2, GROb, MGSA-b, MIP-2a, MIP2}, IRF7 (interferon regulatory factor 7) [NCBI Gene 3665] {aka IMD39, IRF-7, IRF-7H, IRF7A, IRF7B, IRF7C}, COL20A1 (collagen type XX alpha 1 chain) [NCBI Gene 57642], CYTOR (cytoskeleton regulator RNA) [NCBI Gene 112597] {aka C2orf59, LINC00152, NCRNA00152}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, BISPR (BST2 interferon stimulated positive regulator) [NCBI Gene 105221694] {aka lncBST2}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, FOXN3-AS1 (FOXN3 antisense RNA 1) [NCBI Gene 400236], THRIL (TNF and HNRNPL related immunoregulatory long non-coding RNA) [NCBI Gene 102659353] {aka BRI3BP-AS1, BRI3BPAS1, Linc1992, TCONS_00020260}, LEF1 (lymphoid enhancer binding factor 1) [NCBI Gene 51176] {aka ECTD1, ECTD17, LEF-1, TCF10, TCF1ALPHA, TCF7L3}, LINC00487 (long intergenic non-protein coding RNA 487) [NCBI Gene 400941], DOCK8 (dedicator of cytokinesis 8) [NCBI Gene 81704] {aka HEL-205, HIES2, MRD2, ZIR8}, FOXN3 (forkhead box N3) [NCBI Gene 1112] {aka C14orf116, CHES1, PRO1635}, IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}, LINC00189 (long intergenic non-protein coding RNA 189) [NCBI Gene 193629] {aka C21orf109, NCRNA00189}, EGOT (eosinophil granule ontogeny transcript) [NCBI Gene 100126791] {aka EGO, NCRNA00190}, LEF1-AS1 (LEF1 antisense RNA 1) [NCBI Gene 641518] {aka LEF1NAT}, ATP6V0E2-AS1 (ATP6V0E2 antisense RNA 1) [NCBI Gene 401431], IFIH1 (interferon induced with helicase C domain 1) [NCBI Gene 64135] {aka AGS7, Hlcd, IDDM19, IMD95, MDA-5, MDA5}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, FCER1G (Fc epsilon receptor Ig) [NCBI Gene 2207] {aka FCRG}, USP18 (ubiquitin specific peptidase 18) [NCBI Gene 11274] {aka ISG43, PTORCH2, UBP43}, FAM225A (family with sequence similarity 225 member A) [NCBI Gene 286333] {aka C9orf109, LINC00256A, NCRNA00256A}, SERPINB9P1 (serpin family B member 9 pseudogene 1) [NCBI Gene 221756] {aka SERPINB9P}, PTGDR (prostaglandin D2 receptor) [NCBI Gene 5729] {aka AS1, ASRT1, DP, DP1, PTGDR1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, MIR544A (microRNA 544a) [NCBI Gene 664613] {aka MIR544, MIRN544, hsa-mir-544, hsa-mir-544a}, LY6S-AS1 (LY6S antisense RNA 1) [NCBI Gene 286122] {aka C8orf31, LINC02904}, FCN1 (ficolin 1) [NCBI Gene 2219] {aka FCNM}, P2RY13 (purinergic receptor P2Y13) [NCBI Gene 53829] {aka FKSG77, GPCR1, GPR86, GPR94, P2Y13, SP174}, ZAP70 (zeta chain of T cell receptor associated protein kinase 70) [NCBI Gene 7535] {aka ADMIO2, IMD48, SRK, STCD, STD, TZK}, DLEU2 (deleted in lymphocytic leukemia 2) [NCBI Gene 8847] {aka ALT1, BCMSUN, DLB2, LEU2, LINC00022, MIR15AHG}
- **Diseases:** EVD (MESH:D019142), cytotoxicity (MESH:D064420), DM (MESH:D009223), severe immunodeficiency syndrome (MESH:D045169), yellow fever (MESH:D015004), acute myeloid leukemia (MESH:D015470), HIV infection (MESH:D015658), infection (MESH:D007239), hepatocellular carcinoma (MESH:D006528), B cell maturation deficiency (MESH:D015448), COVID-19 (MESH:D000086382), cancer (MESH:D009369), hemorrhagic fever (MESH:D006480), influenza (MESH:D007251), deaths (MESH:D003643), leukemic (MESH:D007938), cutaneous melanoma (MESH:C562393), Sendai virus infection (MESH:D014777), stroke (MESH:D020521), osteosarcoma (MESH:D012516), bacterial infections (MESH:D001424), inflammation (MESH:D007249), dengue (MESH:D003715), Epstein-Barr virus infection (MESH:D020031), B-cell lymphoma (MESH:D016393), TD (MESH:D004409), obesity (MESH:D009765)
- **Chemicals:** MVA (MESH:C051113), H3K27Ac (-)
- **Species:** Homo sapiens (human, species) [taxon 9606], Ebola virus [taxon 186536], Vesicular stomatitis virus (species) [taxon 11276], Mus musculus (house mouse, species) [taxon 10090], Sendai virus [taxon 11191], Hepatitis C Virus [taxon 11103], Zaire ebolavirus (no rank) [taxon 186538], Ebola virus (no rank) [taxon 1570291], Filoviridae (family) [taxon 11266]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12929432/full.md

## References

65 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929432/full.md

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Source: https://tomesphere.com/paper/PMC12929432