Engineered Outer Membrane Vesicles Vaccine Successfully Prevents Experimental Periodontitis

To construct an engineered outer membrane vesicles (OMVs) vaccine encapsulated in metal-polyphenol network (MPN), and assess its effectiveness in enhancing antimicrobial immunity and preventing experimental periodontitis in mouse. The MPN@OMV vaccine was constructed by encapsulating P. gingivalis OMVs with a shell-like structure through the coordination interactions of tannic acid and metal ions. The vaccine's affinity for TLR4 and its in vivo toxicity were assessed. Both in vivo and in vitro immune activation capacity of MPN@OMV were evaluated, and potential mechanisms were explored through transcriptome analysis. To test the vaccine's preventive effects, a mouse periodontitis model was established following preventive immunization. 16S sequencing of saliva was performed to assess the potential impact on the oral flora microenvironment. MPN@OMV reduced stimulation to TLR4 and attenuated the toxicity of high-dose OMV. Furthermore, MPN@OMV promoted DC maturation, T cell proliferation and activation, and significantly increased levels of serum IgG and salivary secretory IgA. Immunoprevention with MPN@OMV successfully decreased alveolar bone resorption, inflammation, and P. gingivalis content in periodontal tissues in mouse. Transcriptome analysis revealed that MPN@OMV enhanced IL17 signaling pathway, leading to increased expression of active factors such as IL17a, IFNγ, and Ccl2. 16S sequencing showed that MPN@OMV can improve the oral flora microenvironment. This direct masking strategy for OMVs enhanced specific antimicrobial immunity while attenuating toxicity and successfully prevented periodontitis, which could be widely used in antimicrobial vaccines for bacterial infectious diseases.