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This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan\u2013catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS\u2010CoV\u20102 spike protein receptor\u2010binding domain (RBD) and toll\u2010like receptor (TLR)9 agonist unmethylated cytosine\u2010guanine (CpG) motif, forming uniform virus\u2010like nanoparticles (Ssp\u2010Chic\u2010RBD\u2010CpG) via electrostatic and covalent interactions. Ssp\u2010Chic\u2010RBD\u2010CpG, mimicking the morphology and function of inactive virions, effectively prolongs the retention time of RBD in the nasal mucosa by 3.92\u2010fold compared to RBD alone, enhances the maturation of dendritic cells (DCs), and facilitates the antigen trafficking to the draining lymph nodes, which subsequently induces a stronger mucosal immunity. Mechanistically, the enhanced chemokine chemokine (C\u2010C motif) ligand 20 (CCL20)\u2010driven DCs recruitment and maturation by Ssp\u2010Chic\u2010RBD\u2010CpG are evidenced by a cell co\u2010culture model. In addition, the overexpression of TLR4\/9 and activation of MYD88\/NF\u2010\u03baB signaling pathway in activation of DCs are observed. Proof of principle is obtained for RBD, but similar delivery mechanisms can be applied in other protein\u2010based subunit vaccines as well when intranasal administration is needed.<\/jats:p>","DOI":"10.1002\/adhm.202401120","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T09:45:08Z","timestamp":1718703908000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pathogen\u2010Mimicking Nanoparticles Based on Rigid Nanomaterials as an Efficient Subunit Vaccine Delivery System for Intranasal Immunization"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3976-860X","authenticated-orcid":false,"given":"Hongping","family":"Wan","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases Control (CIDC) Sichuan Agricultural University  Chengdu 611130 China"},{"name":"Key Laboratory of Animal Disease and Human Health of Sichuan Province 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