A prime/boost strategy using DNA/fowlpox recombinants expressing the genetically attenuated E6 protein as a putative vaccine against HPV-16-associated cancers

Journal of Translational Medicine
Massimiliano BissaAldo Venuti

Abstract

Considering the high number of new cases of cervical cancer each year that are caused by human papilloma viruses (HPVs), the development of an effective vaccine for prevention and therapy of HPV-associated cancers, and in particular against the high-risk HPV-16 genotype, remains a priority. Vaccines expressing the E6 and E7 proteins that are detectable in all HPV-positive pre-cancerous and cancer cells might support the treatment of HPV-related lesions and clear already established tumors. In this study, DNA and fowlpox virus recombinants expressing the E6F47R mutant of the HPV-16 E6 oncoprotein were generated, and their correct expression verified by RT-PCR, Western blotting and immunofluorescence. Immunization protocols were tested in a preventive or therapeutic pre-clinical mouse model of HPV-16 tumorigenicity using heterologous (DNA/FP) or homologous (DNA/DNA and FP/FP) prime/boost regimens. The immune responses and therapeutic efficacy were evaluated by ELISA, ELISPOT assays, and challenge with TC-1* cells. In the preventive protocol, while an anti-E6-specific humoral response was just detectable, a specific CD8(+) cytotoxic T-cell response was elicited in immunized mice. After the challenge, there was a delay in cancer ap...Continue Reading

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Citations

Sep 9, 2016·Immunotherapy·Charu Aggarwal
Feb 25, 2018·Expert Review of Anticancer Therapy·Marcelo Nazário CordeiroAntonio Carlos De Freitas
Jan 16, 2016·Journal of Gynecologic Oncology·Youn Jin Choi, Jong Sup Park
Apr 20, 2019·Frontiers in Immunology·Hao-Fan WangXin-Hua Liang
Dec 15, 2020·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Faezeh SabetSeyed Abdolrahim Rezaee

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Methods Mentioned

BETA
PCR
transfection
enzyme-linked immunosorbent assays

Software Mentioned

GraphPad Prism

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