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000277881 1001_ $$00000-0003-2945-9897$$aSimonis, Alexander$$b0
000277881 245__ $$aPersistent epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages.
000277881 260__ $$a[London]$$bNature Publishing Group UK$$c2025
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000277881 520__ $$aImmune 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.
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000277881 650_7 $$2Other$$aEpigenetic Memory
000277881 650_7 $$2Other$$aG-quadruplex
000277881 650_7 $$2Other$$aH3K27ac
000277881 650_7 $$2Other$$aSARS-Cov-2 mRNA Vaccination
000277881 650_7 $$2Other$$aTrained Innate Immunity
000277881 650_7 $$2NLM Chemicals$$aHistones
000277881 650_7 $$2NLM Chemicals$$aCOVID-19 Vaccines
000277881 650_7 $$2NLM Chemicals$$aCytokines
000277881 650_7 $$2NLM Chemicals$$aRNA, Messenger
000277881 650_7 $$2NLM Chemicals$$amRNA Vaccines
000277881 650_2 $$2MeSH$$aHumans
000277881 650_2 $$2MeSH$$aMacrophages: immunology
000277881 650_2 $$2MeSH$$aMacrophages: metabolism
000277881 650_2 $$2MeSH$$aEpigenesis, Genetic
000277881 650_2 $$2MeSH$$aSARS-CoV-2: immunology
000277881 650_2 $$2MeSH$$aSARS-CoV-2: genetics
000277881 650_2 $$2MeSH$$aCOVID-19: immunology
000277881 650_2 $$2MeSH$$aCOVID-19: prevention & control
000277881 650_2 $$2MeSH$$aHistones: metabolism
000277881 650_2 $$2MeSH$$aHistones: immunology
000277881 650_2 $$2MeSH$$aHistones: genetics
000277881 650_2 $$2MeSH$$aImmunologic Memory
000277881 650_2 $$2MeSH$$aPromoter Regions, Genetic
000277881 650_2 $$2MeSH$$aAcetylation
000277881 650_2 $$2MeSH$$aCOVID-19 Vaccines: immunology
000277881 650_2 $$2MeSH$$aImmunity, Innate
000277881 650_2 $$2MeSH$$aCytokines: metabolism
000277881 650_2 $$2MeSH$$aVaccination
000277881 650_2 $$2MeSH$$aRNA, Messenger: immunology
000277881 650_2 $$2MeSH$$amRNA Vaccines: immunology
000277881 650_2 $$2MeSH$$aEpigenetic Memory
000277881 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE  University of Bonn$$x0
000277881 7001_ $$aTheobald, Sebastian J$$b1
000277881 7001_ $$00009-0003-1593-9715$$aKoch, Anna E$$b2
000277881 7001_ $$00009-0009-4244-8982$$aMummadavarapu, Ram$$b3
000277881 7001_ $$00000-0003-1378-9648$$aMudler, Julie M$$b4
000277881 7001_ $$aPouikli, Andromachi$$b5
000277881 7001_ $$aGöbel, Ulrike$$b6
000277881 7001_ $$00000-0002-2574-9611$$aActon, Richard$$b7
000277881 7001_ $$aWinter, Sandra$$b8
000277881 7001_ $$aAlbus, Alexandra$$b9
000277881 7001_ $$aHolzmann, Dmitriy$$b10
000277881 7001_ $$aAlbert, Marie-Christine$$b11
000277881 7001_ $$aHallek, Michael$$b12
000277881 7001_ $$00000-0002-6312-4591$$aWalczak, Henning$$b13
000277881 7001_ $$0P:(DE-2719)9000845$$aUlas, Thomas$$b14$$udzne
000277881 7001_ $$00000-0002-2962-7814$$aKoch, Manuel$$b15
000277881 7001_ $$00000-0002-6953-9835$$aTessarz, Peter$$b16
000277881 7001_ $$00000-0002-2835-4471$$aHänsel-Hertsch, Robert$$b17
000277881 7001_ $$00000-0001-8351-2690$$aRybniker, Jan$$b18
000277881 773__ $$0PERI:(DE-600)2193510-5$$a10.1038/s44320-025-00093-6$$gVol. 21, no. 4, p. 341 - 360$$n4$$p341 - 360$$tMolecular systems biology$$v21$$x1744-4292$$y2025
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