Tiny packages, big potential: bacterial membrane vesicles in vaccinology

Bacterial membrane vesicles (BMVs) are nanoscale, bilayered proteolipid structures secreted by both Gramnegative and Gram-positive bacteria. Initially considered cellular debris, BMVs are now recognized as evolutionarily conserved entities with critical roles in bacterial communication, immune modulation, virulence factor delivery, and horizontal gene transfer. Their structural and functional resemblance to eukaryotic extracellular vesicles has fueled growing interest in their use as versatile vaccine platforms. Licensed meningococcal OMV vaccines established proof-of-concept for their safety and immunogenicity, and ongoing studies are extending applications to enteric pathogens and viral infections. Recent advances in genetic engineering, glycoengineering, and modular antigen display systems have enabled the design of "plug-and-play" BMVs with reduced reactogenicity and enhanced protective efficacy. In parallel, innovations in bioprocessing and formulation technologies are improving scalability, stability, and delivery, including mucosal routes. This review highlights the immunological properties, translational potential, and key challenges of BMV-based vaccines, with an emphasis on strategies to optimize safety, antigen specificity, and manufacturing for next-generation vaccine development.