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HPV16 mutant E6/E7 construct is protective in mouse model.
Maryam Moazami Goodarzi1, Ghasem Mosayebi2, Ali Ganji2
1Department of Medical Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
BMC Biotechnology
|October 1, 2024
Summary
A novel human papillomavirus type 16 (HPV-16) construct shows promise as a therapeutic vaccine. Recombinant protein delivery induced stronger protection against HPV-16-associated cancers than DNA vaccines in a mouse model.
Area of Science:
- Oncology
- Immunology
- Vaccinology
Background:
- Human papillomavirus type 16 (HPV-16) is a primary cause of cervical, head, and neck cancers.
- Existing HPV-16 treatments have moderate success, driving the need for effective vaccines.
- Research is focused on developing novel therapeutic strategies against HPV-16 infections.
Purpose of the Study:
- To evaluate the immunization potential of a newly designed HPV-16 mutant (m) E6/E7 fusion gene construct.
- To compare the efficacy of DNA vaccine and recombinant protein platforms for HPV-16 therapy.
- To assess the therapeutic effects of different administration strategies in a preclinical mouse model.
Main Methods:
- Designed and produced an HPV-16 mE6/E7 fusion gene construct in DNA and recombinant protein forms.
- Immunized C57BL/6 mice using various strategies: recombinant protein, DNA vaccine, or a combination.
- Assessed immune responses, including peripheral blood mononuclear cells (PBMCs) proliferation, cytokine production (IL-5, IFN-γ), and antibody levels (IgG1, IgG2a).
- Challenged mice with TC-1 tumor cells to evaluate tumor growth, metastasis, and survival rates.
Main Results:
- The mE6/E7 construct demonstrated potential as an HPV-16 therapeutic vaccine candidate.
- Significant increase in interferon-γ (IFN-γ) was observed in groups receiving recombinant protein (Protein/Protein and DNA/Protein).
- Recombinant protein administration (Protein/Protein and DNA/Protein groups) significantly reduced tumor growth compared to control and DNA/DNA groups.
- Groups receiving recombinant protein showed significantly increased survival rates.
Conclusions:
- Recombinant protein delivery of the HPV-16 mE6/E7 construct induced stronger protective immunity than the DNA vaccine.
- Protein/Protein and DNA/Protein administration strategies are promising for developing an effective HPV-16 therapeutic vaccine.
- The study supports the potential of this novel construct for HPV-16 cancer prevention and treatment.
Keywords:
DNA vaccineFusion geneHPV-16Prime-boost strategyRecombinant proteinTherapeutic vaccineTumor-specific antigens (TSAs)
