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, curcumin 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.

中文翻译：

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HPV16/18 L1-L2-E7 多表位融合构建体与姜黄素和纳米姜黄素在 C57BL/6 小鼠模型中的免疫反应和抗肿瘤作用

 目标

人乳头瘤病毒 (HPV) L1、L2 和 E7 蛋白被用作开发预防性和治疗性疫苗的靶抗原。此外，抗原与热休克蛋白（HSP）的连接可以增强疫苗的效力。姜黄素和纳米姜黄素化合物被建议作为癌症的化学预防和化疗剂。在本研究中，使用两种多表位 DNA 和基于肽的疫苗构建体（L1-L2-E7 和 HSP70-L1-L2-E7）以及姜黄素和纳米姜黄素来评估肿瘤小鼠模型中的免疫反应和保护/治疗效果。

 主要方法

首先，将多表位L1-L2-E7和HSP70-L1-L2-E7融合基因亚克隆到真核和原核表达载体中。重组多表位肽是在大肠杆菌菌株中产生的。然后，评估了姜黄素和纳米姜黄素对 HEK-293 T 非癌细胞和 C3 癌细胞的细胞毒性作用。最后，使用不同的方案对小鼠进行疫苗接种。姜黄素和纳米姜黄素化合物单独施用或与不同的疫苗构建体一起施用。

 主要发现

我们的数据表明，使用纳米姜黄素与多表位 HSP70-L1-L2-E7 疫苗结构可以完全保护小鼠免受 HPV 相关 C3 肿瘤细胞的侵害，并在治疗测试中根除肿瘤。此外，纳米姜黄素比单独的姜黄素表现出更高的保护作用。一般来说，姜黄素和纳米姜黄素化合物可以与多表位疫苗构建体协同减少肿瘤生长，但它们不影响不同方案中的免疫反应。

 意义

这些数据表明，设计的多表位疫苗构建体与姜黄素和纳米姜黄素可用作 HPV 疫苗开发的有前景的方法。