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Transl. Med."],"published-print":{"date-parts":[[2025,11,12]]},"abstract":"<jats:p>\n                    Therapeutic vaccines against cervical cancer caused by human papillomavirus (HPV) are still an unmet medical need, despite a prophylactic HPV vaccine being available, and the now-licensed systemic vaccines may have a limited effect on the reproductive tract. To specifically inhibit cervical cancer development, the concept of mucosal immunity based on the reproductive-respiratory axis was adopted to develop a nasal HPV therapeutic vaccine. We used a cationic nanogel for the nasal vaccine delivery system and targeted HPV16 E7, an oncoprotein in HPV-driven cervical cancer to demonstrate the feasibility of a nasal therapeutic vaccine. The vaccine was combined with cyclic di\u2013adenosine monophosphate as a cell-mediated immunity-inducing adjuvant. Intranasal immunization with the nanogel vaccine induced E7-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in mouse cervicovaginal tissue. An antitumor effect due to the infiltration of vaccine-induced E7-specific T cells was also observed in an orthotopic tumor model in mice. Furthermore, intranasal immunization of nonhuman primates with the nanogel vaccine using a spray device that is also applicable to humans induced E7-specific T cells in the reproductive tissues. Our findings demonstrated that this nasal therapeutic vaccine effectively controlled cervical cancer and will contribute to preclinical evidence for clinical testing in the near future.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.ado8840","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T18:58:19Z","timestamp":1762973899000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Cationic nanogel\u2013based nasal therapeutic HPV vaccine prevents the development of cervical cancer"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2657-6185","authenticated-orcid":true,"given":"Rika","family":"Nakahashi-Ouchida","sequence":"first","affiliation":[{"name":"Department of Human Mucosal Vaccinology, Chiba University Hospital, Chuo-ku, Chiba, 260-8670, Japan."},{"name":"Synergy Institute for Futuristic Mucosal Vaccine Research and Development 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