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There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP<jats:sub>366<\/jats:sub>, a nucleoprotein\u2010derived epitope and PA<jats:sub>224<\/jats:sub>, a polymerase acidic subunit derived epitope, are bioengineered. These BP\u2010NP<jats:sub>366<\/jats:sub>\/PA<jats:sub>224<\/jats:sub> can be manufactured at a high yield and are obtained at \u224893% purity, exhibiting ambient\u2010temperature stability. Immunological characterization includes comparing systemic and mucosal immune responses mounted following intramuscular or intranasal immunization. Immunization with BP\u2010NP<jats:sub>366<\/jats:sub>\/PA<jats:sub>224<\/jats:sub> without adjuvant triggers influenza\u2010specific CD8<jats:sup>+<\/jats:sup> T cell priming and memory CD8<jats:sup>+<\/jats:sup> T cell development. Co\u2010delivery with the adjuvant poly(I:C) significantly boosts the size and functionality of the influenza\u2010specific pulmonary resident memory CD8<jats:sup>+<\/jats:sup> T cell pool. Intranasal, but not intramuscular delivery of BP\u2010NP<jats:sub>366<\/jats:sub>\/PA<jats:sub>224<\/jats:sub> with poly(I:C), provides protection against influenza virus challenge. Overall, the BP approach demonstrates as a suitable antigen formulation for intranasal delivery toward induction of systemic protective T cell responses against influenza virus.<\/jats:p>","DOI":"10.1002\/adhm.202304188","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T05:55:05Z","timestamp":1709013305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Intranasal Epitope\u2010Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus"],"prefix":"10.1002","volume":"13","author":[{"given":"Ziyang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne The Peter Doherty Institute for Infection and Immunity  Melbourne Victoria 3000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. 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