{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:44:47Z","timestamp":1789170287984,"version":"build-2803163510"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004008","name":"Istituto Superiore di Sanit\u00e0","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004008","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2032Istruzione, dell\u2032Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>System vaccinology identified an early innate signature associated with vaccine-mediated protection whose induction is likely to involve both immune and non-immune cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To dissect muscle and stromal cell contribution, we simulated\n                      <jats:italic>in vitro<\/jats:italic>\n                      anti-COVID19 BNT162b2 mRNA vaccine intramuscular administration in human primary cell systems composed of 3D muscle-like tissue (3D-MT), fibroblasts, and peripheral blood mononuclear cells (PBMC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BNT162b2 vaccine was recognized by all cell types, although fibroblasts only translated the spike antigen. Factors from vaccine-injected 3D-MT stimulated monocyte and macrophage recruitment and promoted inflammatory macrophage activation, while stromal factors improved dendritic cell frequency and activation. Conditioned media from vaccine-exposed 3D-MT and fibroblasts elicited in PBMC the expression of an early innate immune module previously associated with protective responses in BNT162b2 vaccinees.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Thus, models combining human PBMC, stromal and muscle cells could be employed for the\n                      <jats:italic>in vitro<\/jats:italic>\n                      validation of system vaccinology findings and non-animal vaccine pre-clinical testing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1651095","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T05:29:10Z","timestamp":1760074150000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["A biomimetic 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