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. 2021 Aug 12;15(2):1645–1653. doi: 10.1007/s12274-021-3713-4

Orthogonal modular biosynthesis of nanoscale conjugate vaccines for vaccination against infection

Xin Li 1, Chao Pan 1,✉, Peng Sun 1, Zhehui Peng 1, Erling Feng 1, Jun Wu 1, Hengliang Wang 1,✉, Li Zhu 1,✉
PMCID: PMC8359766  PMID: 34405037

Abstract

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.

graphic file with name 12274_2021_3713_Fig1_HTML.jpg

Electronic Supplementary Material

Supplementary material (Figs. S1–S9) is available in the online version of this article at 10.1007/s12274-021-3713-4.

Keywords: Shigela flexneri 2a, O-polysaccharide, virus-like particle, SpyTag/SpyCatcher system, nanoconjugate vaccines

Electronic Supplementary Material

12274_2021_3713_MOESM1_ESM.pdf (2.3MB, pdf)

Orthogonal modular biosynthesis of nanoscale conjugate vaccines for vaccination against infection

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81930122 and U20A20361) and the National Key Research and Development Project of China (No. 2021YFC2102101).

Contributor Information

Chao Pan, Email: panchaosunny@163.com.

Hengliang Wang, Email: wanghl@bmi.ac.cn.

Li Zhu, Email: jewly54@bmi.ac.cn.

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Supplementary Materials

12274_2021_3713_MOESM1_ESM.pdf (2.3MB, pdf)

Orthogonal modular biosynthesis of nanoscale conjugate vaccines for vaccination against infection

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