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In this study, we designed a nanomaterial-based therapeutic HPV vaccine, comprising manganese (Mn4+)-doped silica nanoparticles (Mn4+-SNPs) and the viral neoantigen peptide GF001 derived from the HPV16 E7 oncoprotein. We show in mice that Mn4+-SNPs act as self-adjuvants by activating the inflammatory signaling pathway via generation of reactive oxygen species, resulting in immune cell recruitment to the immunization site and dendritic cell maturation. Mn4+-SNPs further serve as Ag carriers by facilitating endo\/lysosomal escape via depletion of protons in acidic endocytic compartments and subsequent Ag delivery to the cytosol for cross-presentation. The Mn4+-SNPs+GF001 nanovaccine induced strong E7-specific CD8+ T cell responses, leading to remission of established murine HPV16 E7-expressing solid TC-1 tumors and E7-expressing transgenic skin grafts. This vaccine construct offers a simple and general strategy for therapeutic HPV and potentially other cancer vaccines.<\/jats:p>","DOI":"10.4049\/jimmunol.2000355","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T16:30:23Z","timestamp":1611765023000},"page":"987-998","source":"Crossref","is-referenced-by-count":34,"title":["Manganese-Doped Silica-Based Nanoparticles Promote the Efficacy of Antigen-Specific Immunotherapy"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4456-9480","authenticated-orcid":false,"given":"Janin","family":"Chandra","sequence":"first","affiliation":[{"name":"The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba , Queensland 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9843-0284","authenticated-orcid":false,"given":"Siok 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Assefa","family":"Bashaw","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba , Queensland 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6735-6808","authenticated-orcid":false,"given":"Zewen Kelvin","family":"Tuong","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba , Queensland 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane, Queensland 4072 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