A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in mice.

infection is a severe public health concern with the growing number of multidrug-resistant strains. can circumvent the defense mechanisms of host immunity with the aid of multiple virulence factors. An efficacious multicomponent vaccine targeting diverse immune evasion strategies developed by is thus crucial for its infection control. In this study, we exploited the SpyCatcher-SpyTag system to engineer bacterial outer membrane vesicles (OMVs) for the development of a multitargeting click vaccine. We decorated OMVs with surface exposed SpyCatcher a truncated OmpA(a.a 1-155)-SpyCatcher fusion. The engineered OMVs can flexibly bind with various SpyTag-fused antigens to generate an OMV-based click vaccine. Compared with antigens mixed with alum adjuvant, the click vaccine simultaneously induced more potent antigen-specific humoral and Th1-based cellular immune response, which afforded protection against Newman lethal challenge in a mouse model. Our study provided a flexible and versatile click vaccine strategy with the potential for fighting against emerging clinical isolates.