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Conventional subunit vaccines are limited by suboptimal spatiotemporal dissociation between antigens and adjuvants, as well as insufficient specific targeting, resulting in compromised immunogenicity. Herein, we report a biomimetic nanovaccine platform engineered to overcome these limitations through the synergistic co-delivery of antigen and adjuvant. This platform is constructed by co-displaying the TBE virus envelope protein domain III (fused to a dendritic cell-targeting peptide, Dcpep) together with the molecular adjuvant MAB2560 on the surface of bacterium-like particles (BLPs). The resulting co-display vaccine, EDc2&amp;MAB2560-GEM BLPs, outperforms a simple mixture of its components, inducing significantly higher titers of TBEV-specific IgG antibodies, robust T-cell and B-cell immune responses, and durable immunity in mice. Mechanistic studies reveal that these enhanced immune responses arise from the platform\u2019s ability to precisely co-deliver antigen and adjuvant to dendritic cells, thereby triggering a potent cascading immunostimulatory effect. This work highlights the critical role of spatiotemporal coupling within targeted nanocarriers and establishes a versatile strategy for the development of next-generation subunit vaccines with enhanced potency and safety.<\/jats:p>","DOI":"10.1021\/acsinfecdis.6c00544","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:01:59Z","timestamp":1789549319000},"page":"3487-3501","source":"Crossref","is-referenced-by-count":0,"title":["A Modular Biomimetic\nNanovaccine for TBEV: Orchestrating\nCascade Immunoprotection via Programmed Dendritic Cell Targeting and\nAntigen\u2013Adjuvant Co-delivery"],"prefix":"10.1021","volume":"12","author":[{"given":"NAMES. Yuancheng","family":"Li","sequence":"first","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, China, 130062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunrong","family":"Miao","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, China, 130062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, China, 130062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailun","family":"Li","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, China, 130062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wang","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, China, 130062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Xie","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, China, 130062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualei","family":"Wang","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, China, 130062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-9759","authenticated-orcid":true,"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Jilin University , , ,","place":["Changchun, China, 130062"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"issue":"9627","key":"2026100909094435200_cit1","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1016\/S0140-6736(08)60800-4","article-title":"Tick-borne encephalitis","volume":"371","author":"Lindquist","year":"2008","journal-title":"Lancet"},{"issue":"5","key":"2026100909094435200_cit2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2470","article-title":"Tick-borne\nencephalitis: A comprehensive review of the epidemiology, virology,\nand clinical picture","volume":"33","author":"Chiffi","year":"2023","journal-title":"Rev. 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Clin. Microbiol."},{"issue":"20","key":"2026100909094435200_cit51","doi-asserted-by":"publisher","first-page":"3277","DOI":"10.3390\/diagnostics13203277","article-title":"Recombinant TBEV protein\nE of the Siberian subtype is a candidate antigen in the ELISA test\nsystem for differential diagnosis","volume":"13","author":"Baryshnikova","year":"2023","journal-title":"Diagnostics"},{"key":"2026100909094435200_cit52","doi-asserted-by":"publisher","first-page":"1352720","DOI":"10.3389\/fimmu.2024.1352720","article-title":"Defining the \u201cCorrelate (s)\nof Protection\u201d to tick-borne encephalitis vaccination and infection\u2013key\npoints and outstanding questions","volume":"15","author":"Ackermann-Ga\u0308umann","year":"2024","journal-title":"Front. 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