Design and evaluation of a multi-epitope DNA vaccine against HPV16

Cervical cancer, among the deadliest cancers affecting women globally, primarily arises from persistent infection with high-risk human papillomavirus (HPV). To effectively combat persistent infection and prevent the progression of precancerous lesions into malignancy, a therapeutic HPV vaccine is under development. This study utilized an immunoinformatics approach to predict epitopes of cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs) using the E6 and E7 oncoproteins of the HPV16 strain as target antigens. Subsequently, through meticulous selection of T-cell epitopes and other necessary elements, a multi-epitope vaccine was constructed, exhibiting good immunogenic, physicochemical, and structural characteristics. Furthermore, in silico simulations showed that the vaccine not only interacted well with toll-like receptors (TLR2/TLR3/TLR4), but also induced a strong innate and adaptive immune response characterized by elevated Th1-type cytokines, such as interferon-gamma (IFN-γ) and interleukin-2 (IL2). Additionally, our study investigated the effects of different immunization intervals on immune responses, aiming to optimize a time-efficient immunization program. In animal model experiments, the vaccine exhibited robust immunogenic, therapeutic, and prophylactic effects. Administered thrice, it consistently induced the expansion of specific CD4 and CD8 T cells, resulting in substantial cytokines release and increased proliferation of memory T cell subsets in splenic cells. Overall, our findings support the potential of this multi-epitope vaccine in combating HPV16 infection and signify its candidacy for future HPV vaccine development.

Through the stringent selection of T-cell epitopes and other necessary elements, a novel multi-epitope vaccine targeting HPV 16 E6 and E7 oncoproteins was constructed using an immunoinformatics approach.
The vaccine designed can induce both cellular and humoral immune responses, encompassing all the required immunogenic, physicochemical, and structural characteristics for an ideal vaccine design. Moreover, it offers decent worldwide coverage.
In animal studies, the vaccine demonstrated strong immune responses, including expansion of CD4 and CD8 T cells, cytokine release, and enhanced memory T cell proliferation, resulting in long-term anti-tumor effects, inhibition of tumor growth, and prolonged survival in tumor-bearing mice.
The immunological evaluation of the designed vaccine suggests its potential as a novel vaccine candidate against HPV 16.

Through the stringent selection of T-cell epitopes and other necessary elements, a novel multi-epitope vaccine targeting HPV 16 E6 and E7 oncoproteins was constructed using an immunoinformatics approach.
The vaccine designed can induce both cellular and humoral immune responses, encompassing all the required immunogenic, physicochemical, and structural characteristics for an ideal vaccine design. Moreover, it offers decent worldwide coverage.
In animal studies, the vaccine demonstrated strong immune responses, including expansion of CD4 and CD8 T cells, cytokine release, and enhanced memory T cell proliferation, resulting in long-term anti-tumor effects, inhibition of tumor growth, and prolonged survival in tumor-bearing mice.
The immunological evaluation of the designed vaccine suggests its potential as a novel vaccine candidate against HPV 16.

宫颈癌是全球范围内致死率最高的女性恶性肿瘤之一，其主要病因是高危型人乳头瘤病毒（human papillomavirus, HPV）持续感染。为有效对抗HPV持续感染、阻止癌前病变进展为恶性肿瘤，治疗性HPV疫苗的研发工作正在推进。本研究采用免疫信息学方法，以HPV16型的E6、E7癌蛋白作为靶抗原，预测细胞毒性T淋巴细胞（cytotoxic T lymphocytes, CTLs）与辅助性T淋巴细胞（helper T lymphocytes, HTLs）的表位。随后，通过对T细胞表位及其他必需组分的严谨筛选，构建了一款多表位疫苗，该疫苗展现出良好的免疫原性、理化特性与结构特征。此外，计算机模拟实验显示，该疫苗不仅可与toll样受体（toll-like receptors, TLR2/TLR3/TLR4）高效结合，还可诱导强烈的固有免疫与适应性免疫应答，表现为干扰素-γ（interferon-gamma, IFN-γ）、白细胞介素-2（interleukin-2, IL2）等Th1型细胞因子水平升高。本研究还探讨了不同免疫间隔对免疫应答的影响，旨在优化高效免疫程序。在动物模型实验中，该疫苗展现出优异的免疫原性、治疗与预防效果。以三次免疫方案给药时，其可稳定诱导特异性CD4⁺与CD8⁺T细胞扩增，促使大量细胞因子释放，并提升脾脏细胞中记忆性T细胞亚群的增殖能力。综上，本研究结果支持这款多表位疫苗在对抗HPV16感染中的应用潜力，表明其有望成为未来HPV疫苗研发的候选对象。

通过对T细胞表位及其他必需组分的严谨筛选，本研究采用免疫信息学方法构建了一款靶向HPV16型E6、E7癌蛋白的新型多表位疫苗。
该设计疫苗可同时诱导细胞免疫与体液免疫应答，具备理想疫苗设计所需的全部免疫原性、理化特性与结构特征。此外，该疫苗具备良好的全球人群覆盖性。
在动物实验中，该疫苗可引发强烈免疫应答，包括CD4⁺与CD8⁺T细胞扩增、细胞因子释放以及记忆性T细胞增殖能力增强，进而产生长期抗肿瘤效应、抑制肿瘤生长并延长荷瘤小鼠的存活时间。
针对该设计疫苗的免疫学评价结果显示，其有望成为一款抗HPV16感染的新型疫苗候选物。

通过对T细胞表位及其他必需组分的严谨筛选，本研究采用免疫信息学方法构建了一款靶向HPV16型E6、E7癌蛋白的新型多表位疫苗。
该设计疫苗可同时诱导细胞免疫与体液免疫应答，具备理想疫苗设计所需的全部免疫原性、理化特性与结构特征。此外，该疫苗具备良好的全球人群覆盖性。
在动物实验中，该疫苗可引发强烈免疫应答，包括CD4⁺与CD8⁺T细胞扩增、细胞因子释放以及记忆性T细胞增殖能力增强，进而产生长期抗肿瘤效应、抑制肿瘤生长并延长荷瘤小鼠的存活时间。
针对该设计疫苗的免疫学评价结果显示，其有望成为一款抗HPV16感染的新型疫苗候选物。