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

Yi Pin Chen, Chu Chi Lin, Yu Xin Xie, Chia Yuan Chen, J. Timothy Qiu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)700-705
Number of pages6
JournalTaiwanese Journal of Obstetrics and Gynecology
Volume60
Issue number4
DOIs
Publication statusPublished - Jul 2021

Keywords

  • Cervical cancer
  • cGM-CSF
  • DNA vaccine
  • Human papillomavirus

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Fingerprint

Dive into the research topics of 'Enhancing immunogenicity of HPV16 E<sup>7</sup> DNA vaccine by conjugating codon-optimized GM-CSF to HPV16 E<sup>7</sup> DNA'. Together they form a unique fingerprint.

Cite this