Multidrug-resistant Klebsiella pneumoniae poses a significant threat as a nosocomial pathogen, with no current licensed vaccines available. This study used a mutant E. coli strain expressing exogenous polysaccharides (from K. pneumoniae) to establish glycoengineered generalized modules for membrane antigens (geGMMA) vaccine platform, which demonstrated potent humoral immune responses and protection against K. pneumoniae infections. This approach could lead to safer large-scale vaccine production and promote the development of GMMA vaccines with exogenous bacterial glycan antigens.
Abstract:
Multidrug-resistant Klebsiella pneumoniae constitutes a significant threat as a nosocomial pathogen, and no licensed vaccines are currently available. Generalized modules for membrane antigens (GMMA) have recently been recognized as a promising platform for developing outer membrane vesicle (OMV) vaccines against numerous infectious diseases. The study was carried out in use of the W3110 ΔwbbH-L ΔlpxM::lpxE in which E. coli was treated in order to eliminate the endogenous polysaccharide and use two new ones (polysaccharides from Klebsiella). The exogenous polysaccharides were accurately displayed on the surface of spontaneously released OMVs. The immune responses evoked by subcutaneous administration of these vaccines were evaluated, and the protective effects were assessed using a mouse intraperitoneal challenge model. Interference in the biosynthesis of endogenous polysaccharides (such as deleting related gene clusters) is a viable approach to increasing the yield of glycoengineered GMMA vaccines (geGMMA). The geGMMA platform, which is conducive to safer large-scale production, lays the foundations for the development of GMMA vaccines decorated with exogenous glycan antigens derived from pathogenic bacteria.
Author list:
Jingqin Ye†, Wenhua Huang†, Shujuan Yu, Yan Guo, Peng Sun, Ziyuan Chen, Linhui Hao, Yan Zhang, Caixia Li, Yongqiang Jiang, Jun Wu, Li Zhu*, Hengliang Wang*, Chao Pan*
How to cite:
J. Ye, W. Huang, S. Yu, Y. Guo, P. Sun, Z. Chen, L. Hao, Y. Zhang, C. Li, Y. Jiang, J. Wu, L. Zhu, H. Wang, C. Pan, Exploration 2025, 5, 20240042.
https://doi.org/10.1002/EXP.20240042