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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Immunological Memory

This article is part of the Research TopicDistinctive features of tissue-resident and circulating immune memory cellsView all articles

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

Provisionally accepted
Izabela MamedeIzabela Mamede1Thomaz Lüscher DiasThomaz Lüscher Dias2,3Isabelle Franco MoscardiniIsabelle Franco Moscardini4Patrícia Gonzalez-DiasPatrícia Gonzalez-Dias5Barbara MarinhoBarbara Marinho1Fernando MarconFernando Marcon6Thiago Dominguez Crespo HirataThiago Dominguez Crespo Hirata7Michael EichbergMichael Eichberg8Donata MedagliniDonata Medaglini9Ali M HarandiAli M Harandi10,11Claire-Anne SiegristClaire-Anne Siegrist12Tom H.M. OttenhoffTom H.M. Ottenhoff13Francesco SantoroFrancesco Santoro9André Nicolau Aquime GonçalvesAndré Nicolau Aquime Gonçalves14Rafael B PolidoroRafael B Polidoro15Gloria R. FrancoGloria R. Franco1Paulo P AmaralPaulo P Amaral16*Helder NakayaHelder Nakaya17,3*
  • 1Universidade Federal de Minas Gerais Departamento de Bioquimica e Imunologia, Belo Horizonte, Brazil
  • 2DeepLife, Vernon, France
  • 3Universidade de Sao Paulo Departamento de Analises Clinicas e Toxicologicas, São Paulo, Brazil
  • 4Bios-Therapy, Physiological Systems for Health S.p.A, Sansepolcro, Italy
  • 5Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom
  • 6Laboratory of Genetics and Molecular Cardiology (LGCM) - InCor / HCFMUSP, Sao Paulo, Brazil
  • 7Centre of Omics Technologies (CTO), School of Pharmaceutical Sciences, University of São Paulo, Sao Paulo, Brazil
  • 8Strategic Alliances at Merck Research Laboratories, Philadelphia, United States
  • 9Universita degli Studi di Siena Dipartimento di Biotecnologie Mediche, Siena, Italy
  • 10Department of Microbiology & Immunology, Goteborgs universitet Sahlgrenska Akademin, Gothenburg, Sweden
  • 11Vaccine Evaluation Center, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, Canada
  • 12Center of Vaccinology, Universite de Geneve Departement de pathologie et immunologie, Geneva, Switzerland
  • 13Leids Universitair Medisch Centrum Afdeling Infectieziekten, Leiden, Netherlands
  • 14University of Oxford Department of Paediatrics, Oxford, United Kingdom
  • 15Department of Pediatrics, Indiana University School of Medicine, Indianapolis, United States
  • 16INSPER Institute of Education and Research, Sao Paulo, Brazil
  • 17Hospital Israelita Albert Einstein, São Paulo, Brazil

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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

Keywords: Ebola (EBOV), lncRNA, RNA, systems biology, Vaccine

Received: 29 Aug 2025; Accepted: 12 Dec 2025.

Copyright: © 2025 Mamede, Lüscher Dias, Moscardini, Gonzalez-Dias, Marinho, Marcon, Dominguez Crespo Hirata, Eichberg, Medaglini, Harandi, Siegrist, Ottenhoff, Santoro, Aquime Gonçalves, Polidoro, Franco, Amaral and Nakaya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Paulo P Amaral
Helder Nakaya

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material