Outer membrane vesicles as next-generation vaccine platforms: Mechanisms of antigen presentation

Both pathogenic and commensal Gram-negative bacteria constitutively secrete outer membrane vesicles (OMV), which are non-replicative nanoparticles encapsulating a diverse range of parent bacterial components. Owing to their intrinsic immunogenicity and favorable safety profile, OMV can effectively stimulate innate and adaptive immune responses. In addition to their roles in bacterial survival-such as mediating environmental adaptation, nutrient uptake, intercellular communication, and virulence dissemination-OMV also function as versatile antigen delivery platforms. They preserve the native conformation and immunogenicity of antigens and facilitate efficient antigen presentation via multiple pathways, including direct, cross-presentation, and cross-dressing mechanisms. These properties make OMV promising candidates for vaccine development and antigen delivery applications. Nonetheless, elucidating their precise antigen presentation mechanisms remains a key research challenge. This review summarizes current advances and understanding of OMV-mediated antigen presentation as novel vaccine vectors and aims to provide a theoretical foundation for further research and application in vaccine and antigen delivery systems.