Synthetic Bacterial Membrane Vesicles as Versatile Antigen-Display Platforms against Respiratory Syncytial Virus

Bacterial outer membrane vesicles (OMV) hold promise as vaccine platforms due to their natural adjuvant properties and nanoscale dimensions. However, their inherent inflammatory properties can induce excessive immune reactions, potentially harming the host, while their variability in size and low yield pose challenges for large-scale applications. To address these challenges, we developed synthetic bacterial vesicles (SyBV) through bacterial cell lysis followed by detergent treatment and sonication to eliminate nucleic acids, producing high-purity vesicles with minimal cytoplasmic residue. SyBV triggered comparable antigen-specific adaptive immunity but avoided strong inflammatory responses. We engineered SyBV to display the prefusion F protein (preF) of respiratory syncytial virus (RSV) with cytotoxic lysin A (ClyA). This approach effectively induced preF-specific antibodies and robust immune responses. Our findings suggest that SyBV could provide a safer, more efficient vaccine platform for preventing viral infections, overcoming the limitations associated with traditional OMV while preserving immunogenicity.