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@ARTICLE{Simonis:277881,
      author       = {Simonis, Alexander and Theobald, Sebastian J and Koch, Anna
                      E and Mummadavarapu, Ram and Mudler, Julie M and Pouikli,
                      Andromachi and Göbel, Ulrike and Acton, Richard and Winter,
                      Sandra and Albus, Alexandra and Holzmann, Dmitriy and
                      Albert, Marie-Christine and Hallek, Michael and Walczak,
                      Henning and Ulas, Thomas and Koch, Manuel and Tessarz, Peter
                      and Hänsel-Hertsch, Robert and Rybniker, Jan},
      title        = {{P}ersistent epigenetic memory of {SARS}-{C}o{V}-2 m{RNA}
                      vaccination in monocyte-derived macrophages.},
      journal      = {Molecular systems biology},
      volume       = {21},
      number       = {4},
      issn         = {1744-4292},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DZNE-2025-00501},
      pages        = {341 - 360},
      year         = {2025},
      abstract     = {Immune memory plays a critical role in the development of
                      durable antimicrobial immune responses. How precisely mRNA
                      vaccines train innate immune cells to shape protective host
                      defense mechanisms remains unknown. Here we show that
                      SARS-CoV-2 mRNA vaccination significantly establishes
                      histone H3 lysine 27 acetylation (H3K27ac) at promoters of
                      human monocyte-derived macrophages, suggesting epigenetic
                      memory. However, we found that two consecutive vaccinations
                      were required for the persistence of H3K27ac, which matched
                      with pro-inflammatory innate immune-associated
                      transcriptional changes and antigen-mediated cytokine
                      secretion. H3K27ac at promoter regions were preserved for
                      six months and a single mRNA booster vaccine potently
                      restored their levels and release of macrophage-derived
                      cytokines. Interestingly, we found that H3K27ac at promoters
                      is enriched for G-quadruplex DNA secondary structure-forming
                      sequences in macrophage-derived nucleosome-depleted regions,
                      linking epigenetic memory to nucleic acid structure.
                      Collectively, these findings reveal that mRNA vaccines
                      induce a highly dynamic and persistent training of innate
                      immune cells enabling a sustained pro-inflammatory immune
                      response.},
      keywords     = {Humans / Macrophages: immunology / Macrophages: metabolism
                      / Epigenesis, Genetic / SARS-CoV-2: immunology / SARS-CoV-2:
                      genetics / COVID-19: immunology / COVID-19: prevention $\&$
                      control / Histones: metabolism / Histones: immunology /
                      Histones: genetics / Immunologic Memory / Promoter Regions,
                      Genetic / Acetylation / COVID-19 Vaccines: immunology /
                      Immunity, Innate / Cytokines: metabolism / Vaccination /
                      RNA, Messenger: immunology / mRNA Vaccines: immunology /
                      Epigenetic Memory / Epigenetic Memory (Other) / G-quadruplex
                      (Other) / H3K27ac (Other) / SARS-Cov-2 mRNA Vaccination
                      (Other) / Trained Innate Immunity (Other) / Histones (NLM
                      Chemicals) / COVID-19 Vaccines (NLM Chemicals) / Cytokines
                      (NLM Chemicals) / RNA, Messenger (NLM Chemicals) / mRNA
                      Vaccines (NLM Chemicals)},
      cin          = {AG Schultze / PRECISE},
      ddc          = {570},
      cid          = {I:(DE-2719)1013038 / I:(DE-2719)1013031},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354) / 352
                      - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-352},
      experiment   = {EXP:(DE-2719)PRECISE-20190321},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40133533},
      pmc          = {pmc:PMC11965535},
      doi          = {10.1038/s44320-025-00093-6},
      url          = {https://pub.dzne.de/record/277881},
}