PDF(Pubmed)
Abstract：
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.
摘要：
宫颈癌,在全球影响女性的最致命癌症中，主要起因于高危型人乳头瘤病毒(HPV)的持续性感染.有效对抗持续性感染，防止癌前病变进展为恶性肿瘤，治疗性HPV疫苗正在开发中。这项研究利用免疫信息学方法，以HPV16菌株的E6和E7癌蛋白为靶抗原，预测细胞毒性T淋巴细胞（CTL）和辅助T淋巴细胞（HTL）的表位。随后，通过精心选择T细胞表位和其他必要元件，构建了多表位疫苗，表现出良好的免疫原性，物理化学,和结构特征。此外，计算机模拟表明，该疫苗不仅与toll样受体(TLR2/TLR3/TLR4)相互作用良好，但也诱导了以升高的Th1型细胞因子为特征的强烈的先天和适应性免疫应答，例如干扰素-γ(IFN-γ)和白细胞介素-2(IL2)。此外,我们的研究调查了不同免疫间隔对免疫反应的影响，旨在优化省时的免疫计划。在动物模型实验中,疫苗表现出强大的免疫原性，治疗性的,和预防效果。管理三次，它持续诱导特异性CD4和CD8T细胞的扩增，导致大量细胞因子释放和脾细胞中记忆T细胞亚群的增殖增加。总的来说,我们的研究结果支持了这种多表位疫苗在对抗HPV16感染方面的潜力,并表明其可用于未来HPV疫苗开发.
通过对T细胞表位和其他必要元件的严格选择，使用免疫信息学方法构建了一种靶向HPV16E6和E7癌蛋白的新型多表位疫苗.设计的疫苗可以诱导细胞和体液免疫反应，包括所有必需的免疫原性，物理化学,和理想疫苗设计的结构特征。此外，它提供了体面的全球报道。在动物研究中,疫苗表现出强烈的免疫反应，包括CD4和CD8T细胞的扩增，细胞因子释放，增强记忆T细胞增殖，产生长期的抗肿瘤作用，抑制肿瘤生长，和延长荷瘤小鼠的生存期。设计的疫苗的免疫学评估表明其作为针对HPV16的新型候选疫苗的潜力。
通过对T细胞表位和其他必要元件的严格选择，使用免疫信息学方法构建了一种靶向HPV16E6和E7癌蛋白的新型多表位疫苗.设计的疫苗可以诱导细胞和体液免疫反应，包括所有必需的免疫原性，物理化学,和理想疫苗设计的结构特征。此外，它提供了体面的全球报道。在动物研究中,疫苗表现出强烈的免疫反应，包括CD4和CD8T细胞的扩增，细胞因子释放，增强记忆T细胞增殖，产生长期的抗肿瘤作用，抑制肿瘤生长，和延长荷瘤小鼠的生存期。设计的疫苗的免疫学评估表明其作为针对HPV16的新型候选疫苗的潜力。
