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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.


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Orthogonal modular biosynthesis of nanoscale conjugate vaccines for vaccination against infection

Show Author's information Xin LiChao Pan( )Peng SunZhehui PengErling FengJun WuHengliang Wang( )Li Zhu( )
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of BiotechnologyBeijing 100071 China

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.

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

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Publication history
Copyright
Acknowledgements

Publication history

Received: 16 April 2021
Revised: 17 June 2021
Accepted: 24 June 2021
Published: 12 August 2021
Issue date: February 2022

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2021

Acknowledgements

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).

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