Enhancing immunogenicity of HPV16 E7 DNA vaccine by conjugating codon-optimized GM-CSF to HPV16 E7 DNA

• Main Authors: Yi-Pin Chen (Author), Chu-Chi Lin (Author), Yu-Xin Xie (Author), Chia-Yuan Chen (Author), J. Timothy Qiu (Author)
• Format: Book
• Published: Elsevier, 2021-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1028-4559; 10.1016/j.tjog.2021.05.020
• Keywords: Human papillomavirus; Cervical cancer; cGM-CSF; DNA vaccine; Gynecology and obstetrics; RG1-991
• Source: Taiwanese Journal of Obstetrics & Gynecology, Vol 60, Iss 4, Pp 700-705 (2021)

Objective: To generate immunity against human papillomavirus (HPV), the use of a recombinant DNA vaccine to carry an appropriate target gene is a promising and cost-effective approach. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent immunomodulatory cytokine that enhances the efficacy of vaccines by promoting the development and prolongation of humoral and cellular immunity. In this study, we linked codon-optimized GM-CSF (cGM-CSF) to the HPV16 E7 sequence as fused protein and evaluated the immunogenic potential of this DNA vaccine. Materials and methods: We have demonstrated that cGM-CSF enhanced immunity against tumor challenges by generating and promoting the proliferation of HPV16 E7-specific CD8+ T cells, which secrete IFN-γ in the murine model. In this study, we aimed to evaluate the immunogenic potential of DNA vaccine that constructed by linking codon-optimized GM-CSF to HPV16 E7 sequence in the animal model. We study the half-life of RNA decay and cellular location of HPV16 E7 by Q-PCR and Western blot. We also assess immune response in the animal model by flow cytometry and ELISA. Results: The cGM-CSF-E7 sequence increased and extended the expression of E7 mRNA, in comparison with the E7 sequence alone. Mice vaccinated with the cGM-CSF-E7 DNA vaccine exhibited a slower rate of tumor growth than those vaccinated with the unconjugated E7 DNA vaccine. We also found that the CD4 and CD8+ T cells from these mice showed strong secretion of IFN-γ. Conclusion: Through in vivo antibody depletion experiments, we demonstrated that both CD4+ and CD8+ T cells play an important role in the suppression of tumor growth.