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However, suboptimal antigen bioavailability and rapid systemic clearance remain key barriers to achieving robust vaccine efficacy. Here, we engineer an oral biohybrid vaccine using pH\u2010responsive biomineralized\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    (B\u2010BS\/E7@M) to establish gut\u2010based antigen factories for sustained HPV16 E7 production. The calcium phosphate mineral coating confers gastric acid resistance (78.9% survivability vs. 9.1% uncoated) and synergizes with probiotic\u2010mucosa interactions to prolong intestinal retention (96 h, 4 \u00d7 controls), enabling &gt;4\u2010day antigen persistence and markedly enhances oral bioavailability. This system elicits coordinated immune activation: mucosal priming through germinal center expansion and APC maturation elevates IgG, IgA, and T\u2010cell subsets\u2014including total T cells, cytotoxic T cells, and effector memory T cells\u2014from day 21 onward. Systemic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell activation via cross\u2010presentation enhances central and effector memory T cells, promoting tumor infiltration and resulting in 64% tumor suppression (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001) with 50% complete remission in TC\u20101 models. Mechanistic studies pinpoint gut\u2010orchestrated cytotoxic T cell clonal expansion as the dominant effector pathway. By bridging synthetic biology with stimuli\u2010responsive biomaterials, this work pioneers a paradigm of living biotherapeutics\u2014self\u2010replicating, mucosa\u2010deployable systems for precision cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.202510404","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T06:11:10Z","timestamp":1767420670000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["pH\u2010Responsive Biomineralized Probiotic for Self\u2010Amplifying Mucosal Vaccination: Gut\u2010Engineered Antigen Factories Drive Targeted Cervical Tumor Regression"],"prefix":"10.1002","volume":"38","author":[{"given":"Donglin","family":"Xia","sequence":"first","affiliation":[{"name":"Institute For Applied Research in Public Health School of Public Health Nantong University  Nantong Jiangsu 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