A Purely Biomanufactured System for Delivering Nanoparticles and STING Agonists.

Nanovaccines have significantly contributed in the prevention and treatment of diseases. However, most of these technologies rely on chemical or hybrid semibiological synthesis methods, which limit the manufacturing performance advantages and improved inoculation outcomes compared with traditional vaccines. Herein, a universal and purely biological nanovaccine system is reported. This system integrates three modules: (1) self-assembling nanoparticles, (2) self-catalyzed synthesis of small-molecule stimulator of interferon gene (STING) agonists, and (3) delivery vectors that target the cytosolic surveillance system. Various nanoparticles are efficiently self-assembled using this system. After confirming the excellent immunostimulatory and lymph node targeting of this system, its broad-spectrum antiviral efficacy is further demonstrated. By leveraging the comprehensive biosynthetic capabilities of bacterial cells, this system can efficiently combine various adjuvant-active modular components and antigenic cargo, thereby providing a highly diversified and potent vaccine platform.