Immunological responses and anti-tumor effects of HPV16/18 L1-L2-E7 multiepitope fusion construct along with curcumin and nanocurcumin in C57BL/6 mouse model

LIFE SCIENCES

卷:285

Article

Kayyal, Matin¹  Bolhassani, Azam²  Noormohammadi, Zahra¹  Sadeghizadeh, Majid³ 

[1] Islamic Azad Univ, Dept Biol, Sci & Res Branch, Tehran, Iran

[2] Pasteur Inst Iran, Dept Hepatitis & AIDS, Tehran, Iran

[3] Tarbiat Modares Univ Tehran, Fac Biol Sci, Dept Genet, Tehran, Iran

关键词: Human papillomavirus;    Curcumin;    Nanocurcumin;    Multiepitope vaccine;    Immunotherapy;    Chemotherapy;   

DOI  :  10.1016/j.lfs.2021.119945

来源: Elsevier

【 摘 要 】

Aims: Human papillomavirus (HPV) L1, L2 and E7 proteins were used as target antigens for development of preventive and therapeutic vaccines. Moreover, linkage of antigens to heat shock proteins (HSPs) could enhance the potency of vaccines. Curcumin and nanocurcumin compounds were suggested as the chemopreventive and chemotherapeutic agents against cancer. In this study, two multiepitope DNA and peptide-based vaccine constructs (L1-L2-E7 and HSP70-L1-L2-E7) were used along with curcumin and nanocurcumin to evaluate immune responses, and protective/therapeutic effects in tumor mouse model. Main methods: At first, the multiepitope L1-L2-E7 and HSP70-L1-L2-E7 fusion genes were subcloned in eukaryotic and prokaryotic expression vectors. The recombinant multiepitope peptides were generated in E. coli strain. Then, the cytotoxic effects of curcumin and nanocurcumin were evaluated on HEK-293 T non-cancerous and C3 cancerous cells. Finally, mice vaccination was performed using different regimens. Curcumin and nanocurcumin compounds were administered alone or along with different vaccine constructs. Key findings: Our data indicated that the use of nanocurcumin along with the multiepitope HSP70-L1-L2-E7 vaccine construct could completely protect mice against HPV-related C3 tumor cells, and eradicate tumors in a therapeutic test. Furthermore, nanocurcumin showed higher protection than curcumin alone. Generally, cur cumin and nanocurcumin compounds could reduce tumor growth synergistically with the multiepitope vaccine constructs, but they did not influence the immune responses in different regimens. Significance: These data demonstrated that the designed multiepitope vaccine constructs along with curcumin and nanocurcumin can be used as a promising method for HPV vaccine development.

【 授权许可】

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