Modular design of Salmonella Typhimurium OMV-based nanovaccines for tunable dual-form polysaccharide antigen delivery
- 1College of Veterinary Medicine, Southwest University, Beibei, Chongqing, China
- 2College of Veterinary Medicine, Shandong Agricultural University, Taian, Shandong, China
Abstract
Bacterial diseases are primarily managed with antibiotics, but vaccination is widely acknowledged as the most efficacious strategy for their prevention. Bacterial polysaccharides serve as key protective antigens in hosts and are therefore consistently prioritized as targets for bacterial vaccine development. Polysaccharide-conjugated vaccines have emerged as a promising and effective approach to combat multidrug-resistant bacteria. In order to construct a vaccine carrier capable of delivering bacterial polysaccharides while inducing robust immune response, this study utilized outer membrane vesicles (OMVs) derived from Salmonella Typhimurium as the vaccine carrier instead of the traditional adjuvant components to enhance the immunogenicity of polysaccharide vaccine. S. Typhimurium was genetically engineered to enable the controlled synthesis of LPS and glycoprotein, which were encapsulated within OMVs as two distinct polysaccharide vaccine formulations. This engineered delivery system was used to deliver the O-antigen polysaccharide of Shigella flexneri 3a, and subsequent validation in a murine model further confirmed that its ability to elicit an effective in vivo immune response. The polysaccharide delivery carrier platform established in this study provides a foundation for the subsequent multi-form delivery of bacterial polysaccharides in next-generation biological vaccines. Author summary: The vaccine platform can standardize the induction of immune responses in the body with high safety and low adverse reactions. Its design also allows for the easy switching of the displayed antigens, thereby achieving high efficacy and wide adaptability. The mutant strain of Salmonella Typhimurium constructed in this study can successfully control the synthesis of O antigen polysaccharide LPS and glycoproteins by adding inducers. This enables the O antigen polysaccharide of the bacteria to serve as a polysaccharide substrate for the synthesis of both LPS and glycoproteins, achieving the purpose of artificially intervening in the delivery form of OMVs. Moreover, by replacing the expression plasmids of polysaccharide antigens and peptide antigens, this vaccine platform can achieve adaptability and universality for different bacterial antigens, providing a foundation for the development of vaccines for different bacteria. Finally, through animal experiments, it has been confirmed that the controllable OMVs-based polysaccharide vaccine delivery platform constructed in this study can effectively induce the production of specific antibody levels in the body, thereby exerting immune protection effects, and at the same time, it has excellent biological safety.
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BibTeX
@article{li2026modular,
title = {{Modular design of Salmonella Typhimurium OMV-based nanovaccines for tunable dual-form polysaccharide antigen delivery}},
author = {Mengru Li and Kai Zhou and Meihong Lei and Huanhuan Cao and Xinyu Liu and Shan Li and Ruida Wu and Ming Yang and Xiaoping Bian and Longlong Cao and Qingke Kong},
journal = {PLOS Pathogens},
year = {2026},
month = nov,
doi = {10.1371/journal.ppat.1014781},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014781},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Modular design of Salmonella Typhimurium OMV-based nanovaccines for tunable dual-form polysaccharide antigen delivery
AU - Mengru Li
AU - Kai Zhou
AU - Meihong Lei
AU - Huanhuan Cao
AU - Xinyu Liu
AU - Shan Li
AU - Ruida Wu
AU - Ming Yang
AU - Xiaoping Bian
AU - Longlong Cao
AU - Qingke Kong
PY - 2026
DA - 2026/11/04
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014781
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014781
AB - Bacterial diseases are primarily managed with antibiotics, but vaccination is widely acknowledged as the most efficacious strategy for their prevention. Bacterial polysaccharides serve as key protective antigens in hosts and are therefore consistently prioritized as targets for bacterial vaccine development. Polysaccharide-conjugated vaccines have emerged as a promising and effective approach to combat multidrug-resistant bacteria. In order to construct a vaccine carrier capable of delivering bacterial polysaccharides while inducing robust immune response, this study utilized outer membrane vesicles (OMVs) derived from Salmonella Typhimurium as the vaccine carrier instead of the traditional adjuvant components to enhance the immunogenicity of polysaccharide vaccine. S. Typhimurium was genetically engineered to enable the controlled synthesis of LPS and glycoprotein, which were encapsulated within OMVs as two distinct polysaccharide vaccine formulations. This engineered delivery system was used to deliver the O-antigen polysaccharide of Shigella flexneri 3a, and subsequent validation in a murine model further confirmed that its ability to elicit an effective in vivo immune response. The polysaccharide delivery carrier platform established in this study provides a foundation for the subsequent multi-form delivery of bacterial polysaccharides in next-generation biological vaccines. Author summary: The vaccine platform can standardize the induction of immune responses in the body with high safety and low adverse reactions. Its design also allows for the easy switching of the displayed antigens, thereby achieving high efficacy and wide adaptability. The mutant strain of Salmonella Typhimurium constructed in this study can successfully control the synthesis of O antigen polysaccharide LPS and glycoproteins by adding inducers. This enables the O antigen polysaccharide of the bacteria to serve as a polysaccharide substrate for the synthesis of both LPS and glycoproteins, achieving the purpose of artificially intervening in the delivery form of OMVs. Moreover, by replacing the expression plasmids of polysaccharide antigens and peptide antigens, this vaccine platform can achieve adaptability and universality for different bacterial antigens, providing a foundation for the development of vaccines for different bacteria. Finally, through animal experiments, it has been confirmed that the controllable OMVs-based polysaccharide vaccine delivery platform constructed in this study can effectively induce the production of specific antibody levels in the body, thereby exerting immune protection effects, and at the same time, it has excellent biological safety.
SN - 1553-7374
ER -