Conjugate vaccines represent one of the most effective means for controlling the occurrence of bacterial diseases. Although nanotechnology has been greatly applied in the field of vaccines, it is seldom used for conjugate vaccine research because it is very difficult to connect polysaccharides and nanocarriers. In this work, an orthogonal and modular biosynthesis method was used to produce nanoconjugate vaccines using the SpyTag/SpyCatcher system. When SpyTag/SpyCatcher system is combined with protein glycosylation technology, bacterial O-polysaccharide obtained from Shigela flexneri 2a can be conjugated onto the surfaces of different virus-like particles (VLPs) in a biocompatible and controlled manner. After confirming the excellent lymph node targeting and humoral immune activation abilities, these nanoconjugate vaccines further induced efficient prophylactic effects against infection in a mouse model. These results demonstrated that natural polysaccharide antigens can be easily connected to VLPs to prepare highly efficient nanoconjugate vaccines. To the best of the researchers' knowledge, this is the first time VLP-based nanoconjugate vaccines are produced efficiently, and this strategy could be applied to develop various pathogenic nanoconjugate vaccines. ELECTRONIC SUPPLEMENTARY MATERIAL Supplementary material (Figs. S1-S9) is available in the online version of this article at 10.1007/s12274-021-3713-4.

中文翻译：

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用于感染疫苗接种的纳米级结合疫苗的正交模块化生物合成。

结合疫苗是控制细菌性疾病发生的最有效手段之一。尽管纳米技术在疫苗领域得到了很大的应用，但由于多糖与纳米载体的连接难度很大，因此很少用于结合疫苗的研究。在这项工作中，使用正交和模块化生物合成方法使用 SpyTag/SpyCatcher 系统生产纳米结合疫苗。当 SpyTag/SpyCatcher 系统与蛋白质糖基化技术相结合时，从 Shigela flexneri 2a 获得的细菌 O-多糖可以以生物相容和可控的方式结合到不同病毒样颗粒 (VLP) 的表面。在确认了出色的淋巴结靶向和体液免疫激活能力后，这些纳米结合疫苗在小鼠模型中进一步诱导了针对感染的有效预防效果。这些结果表明，天然多糖抗原可以很容易地连接到 VLPs 以制备高效的纳米结合疫苗。据研究人员所知，这是首次高效生产基于 VLP 的纳米结合疫苗，该策略可用于开发各种致病性纳米结合疫苗。电子补充材料补充材料（图 S1-S9）可在本文的在线版本中找到，网址为 10.1007/s12274-021-3713-4。据研究人员所知，这是首次高效生产基于 VLP 的纳米结合疫苗，该策略可用于开发各种致病性纳米结合疫苗。电子补充材料补充材料（图 S1-S9）可在本文的在线版本中找到，网址为 10.1007/s12274-021-3713-4。据研究人员所知，这是首次高效生产基于 VLP 的纳米结合疫苗，该策略可用于开发各种致病性纳米结合疫苗。电子补充材料补充材料（图 S1-S9）可在本文的在线版本中找到，网址为 10.1007/s12274-021-3713-4。