Modular design of Salmonella Typhimurium OMV-based nanovaccines for tunable dual-form polysaccharide antigen delivery

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.