Qiu Jingxuan, Wei Yiwen, Shu Jiayi, Zheng Wenjing, Zhang Yuxi, Xie Junting, Zhang Dong, Luo Xiaochuan, Sun Xiulan, Wang Xin, Wang Sijie, Wang Xuanyi, Qiu Tianyi
School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
Institute of Clinical Science, Clinical Center of Biotherapy, Zhongshan Hospital, Shanghai Institute of Infectious Disease and Biosecurity, Intelligent Medicine Institute, Shanghai Medical College, Fudan University, 200032, Shanghai, China.
Virol J. 2025 May 27;22(1):166. doi: 10.1186/s12985-025-02796-6.
Norovirus (NoVs) is a foodborne pathogen that causes acute gastroenteritis. The diversity of its principal antigenic protein poses a significant challenge to vaccine development and the prevention of large-scale outbreaks globally. Currently, no licensed vaccines against norovirus have been approved.
We developed a novel pipeline that integrates multiple bioinformatics tools to design broad-spectrum vaccines against NoVs. Specifically, broad-spectrum T-cell epitope vaccines were designed based on consensus sequences and optimized epitope screening, while broad-spectrum B-cell spatial epitope vaccines were constructed using high-throughput antigenicity calculations and epitope mapping.
This pipeline underwent rigorous validation at three levels: firstly, In silico validation: Analysis of properties and structures demonstrated the appropriateness of amino acid composition and the structural integrity of the vaccine sequences. Secondly, theoretical assessment: Evaluation of human leukocyte antigen (HLA) subtype and antigenicity coverage indicated a broad theoretical protective spectrum for the designed vaccine immunogens. Furthermore, in silico simulation confirmed their ability to elicit an immune response. Finally, animal-level validation: Experiments in mice showed that both vaccine immunogens stimulated high levels of IgG and IgA. Notably, Vac-B induced a strong IgG response against GII.2 and a robust IgA response against GII.17, comparable to the immune response elicited by the wild-type NoV non-replicating virus-like particle (VLP) protein group.
Both in silico and in vivo experimental findings suggest that the proposed pipeline and vaccine immunogens could serve as valuable theoretical guidance for the development of multi-epitope vaccines against NoVs.
诺如病毒（NoVs）是一种食源性病原体，可引起急性肠胃炎。其主要抗原蛋白的多样性对疫苗研发及全球大规模疫情的防控构成了重大挑战。目前，尚无针对诺如病毒的获批许可疫苗。
我们开发了一种整合多种生物信息学工具的新型流程，用于设计针对诺如病毒的广谱疫苗。具体而言，基于共有序列和优化的表位筛选设计了广谱T细胞表位疫苗，同时利用高通量抗原性计算和表位图谱构建了广谱B细胞空间表位疫苗。
该流程在三个层面进行了严格验证：其一，计算机模拟验证：对特性和结构的分析表明疫苗序列的氨基酸组成合适且结构完整。其二，理论评估：对人类白细胞抗原（HLA）亚型和抗原性覆盖范围的评估表明，所设计的疫苗免疫原具有广泛的理论保护谱。此外，计算机模拟证实了它们引发免疫反应的能力。最后，动物水平验证：在小鼠身上进行的实验表明，两种疫苗免疫原均刺激产生了高水平的IgG和IgA。值得注意的是，Vac-B诱导了针对GII.2的强烈IgG反应以及针对GII.17的强劲IgA反应，与野生型诺如病毒非复制性病毒样颗粒（VLP）蛋白组引发的免疫反应相当。
计算机模拟和体内实验结果均表明，所提出的流程和疫苗免疫原可为开发针对诺如病毒的多表位疫苗提供有价值的理论指导。
