{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T09:04:09Z","timestamp":1784019849483,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NCI Specialized Program of Research Excellence (SPORE) in Cervical Cancer","award":["NIH\/NCI P50CA098252"],"award-info":[{"award-number":["NIH\/NCI P50CA098252"]}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["R01CA295696"],"award-info":[{"award-number":["R01CA295696"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["R21DE034547"],"award-info":[{"award-number":["R21DE034547"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Persistent infection with high-risk human papillomavirus (HPV), particularly HPV16, is a major driver of HPV-associated cancers; however, strategies for treating established HPV-induced tumors remain scarce. Here, we developed a DNA-based vaccine linking the SARS-CoV-2 spike (S) protein with an HPV16 E7 epitope (aa 49-57) to simultaneously induce antiviral humoral immunity and antitumor cellular responses. We generated 2 constructs, S-E7 and S-RE7, with the latter incorporating a furin cleavage site (R) to enhance antigen processing. In vitro, S-RE7 significantly enhanced E7-specific CD8+ T cell activation compared to S-E7, highlighting the importance of the furin sequence. In vivo, both S-linked vaccines elicited robust E7-specific CD8+ T cell responses and provided complete protection against TC-1 tumor challenge in a prophylactic murine model, with long-lasting immunity upon tumor rechallenge. In therapeutic settings, vaccination with S-E7 or S-RE7 significantly suppressed tumor growth, extended survival, and reduced circulating myeloid-derived suppressor cells (MDSCs), indicating alleviation of systemic immunosuppression. Notably, S-RE7 demonstrated faster antitumor effects overall in early tumor progression. In addition to cellular immunity, both constructs induced high levels of anti-spike antibodies, with S-RE7 eliciting approximately fourfold higher responses than S-E7. Furthermore, S-RE7 effectively boosted pre-existing anti-spike immunity in mice that were previously vaccinated. This \u201ctwo-in-one\u201d strategy represents a promising and versatile platform for the prevention and treatment of HPV-associated cancers while maintaining preparedness against potential SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/ijms27146249","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T08:04:31Z","timestamp":1784016271000},"page":"6249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Spike-Linked HPV16 E7 DNA Vaccine Induces Potent Antitumor and Anti-Spike Immune Responses"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5321-8284","authenticated-orcid":false,"given":"Yichu","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yining","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD 21287, USA"},{"name":"Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Cheng","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Chea","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9993-8004","authenticated-orcid":false,"given":"Chuan-Hsiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD 21287, USA"},{"name":"Department of Cell Biology, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzyy-Choou","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD 21287, USA"},{"name":"Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"},{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"},{"name":"Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Fu","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD 21287, USA"},{"name":"Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41392-024-02083-w","article-title":"Roles of human papillomavirus in cancers: Oncogenic mechanisms and clinical use","volume":"10","author":"Zhang","year":"2025","journal-title":"Signal Transduct. 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