title: Intravaginal HPV DNA vaccination with electroporation induces local CD8+ T-cell immune responses and antitumor effects against cervicovaginal tumors.
abstract: Therapeutic human papillomavirus (HPV) vaccines have the potential to inhibit the progression of an established HPV infection to precancer and cancer lesions by targeting HPV oncoproteins. We have previously developed a therapeutic DNA vaccine encoding calreticulin (CRT) linked to E7, CRT/E7 DNA vaccine, for use in the treatment of HPV-associated lesions. Since the transfection efficiency of DNA vaccines administered in vivo is typically low, we examined the use of electroporation as well as different routes of administration to enhance antigen-specific tumor control. We tested the effects of the CRT/E7 DNA vaccine administered intramuscularly or intravaginally, with or without electroporation, on the generation of CD8+ T-cell immunity and therapeutic antitumor effects in HPV16 E7-expressing cervicovaginal tumor-bearing mice. We found that intravaginal vaccination of CRT/E7 DNA followed by electroporation-induced potent E7-specific CD8(+) T-cell responses in the cervicovaginal tract, compared with intramuscular injection followed by electroporation. Furthermore, tumor-bearing mice vaccinated intravaginally followed by electroporation had an enhanced survival, antitumor effects and local production of IFN-γ+CD8+ T cells compared with those vaccinated intramuscularly with electroporation. Thus, we show that intravaginal CRT/E7 DNA vaccination followed by electroporation generates the most potent therapeutic antitumor effects against an orthotopic E7-expressing tumor model. The current study will have significant clinical implications once a clinically applicable electroporation device for intravaginal use becomes available.
authors: 1] Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China [2] Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors: Y
authors: Y
authors: Sun
authors: Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors: S
authors: S
authors: Peng
authors: 1] Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA [2] Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital of Tongji University Shanghai, Shanghai, China.
authors: J
authors: J
authors: Qiu
authors: 1] Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA [2] Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China [3] Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: J
authors: J
authors: Miao
authors: Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors: B
authors: B
authors: Yang
authors: Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors: J
authors: J
authors: Jeang
authors: 1] Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA [2] Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors: C-F
authors: CF
authors: Hung
authors: 1] Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA [2] Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA [3] Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, USA [4] Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors: T-C
authors: TC
authors: Wu
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D018274:Electroporation / Q000379:methods; D005260:Female; D008810:Mice, Inbred C57BL; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA