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To address these issues, an infection\u2010mimicking gel (IM\u2010Gel) is developed that is designed to emulate the spatiotemporal dynamics of immune stimulation in acute viral infections through in situ supramolecular self\u2010assembly of nanoparticulate\u2010TLR7\/8a (NP\u2010TLR7\/8a) and an antigen with tannic acid (TA). Through collagen\u2010binding properties of TA, the IM\u2010Gel enables sustained delivery and enhanced retention of NP\u2010TLR7\/8a and protein antigen in the lymph node subcapsular sinus of mice for over 7 days, prolonging the exposure of vaccine components in both B cell and T cell zones, leading to robust humoral and cellular responses. The IM\u2010Gel system with the influenza A antigen confers cross\u2010protection against multiple influenza subtypes (H1N1, H5N2, H3N2, H7N3, and H9N2) with long\u2010term immune responses. Combination of the IM\u2010Gel with the SARS\u2010CoV\u20102 spike protein also elicits strong cross\u2010reactive antibody responses against multiple SARS\u2010CoV\u20102 variants (Alpha, Beta, NY510+D614G, Gamma, Kappa, and Delta). The IM\u2010Gel, as a programmable immunomodulatory material, provides a vaccine design principle for the development of next\u2010generation universal vaccines that can elicit broad and durable protective immunity against emerging viruses.<\/jats:p>","DOI":"10.1002\/advs.202412116","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T14:29:15Z","timestamp":1736778555000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatiotemporal Dynamic Immunomodulation by Infection\u2010Mimicking Gels Enhances Broad and Durable Protective Immunity Against Heterologous Viruses"],"prefix":"10.1002","volume":"12","author":[{"given":"Seung Mo","family":"Jin","sequence":"first","affiliation":[{"name":"SKKU Advanced Institute of Nanotechnology (SAINT) Department of Nano Engineering Department of Nano Science and Technology School of Chemical Engineering Biomedical Institute for Convergence at SKKU 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