A Purely Biomanufactured System for Delivering Nanoparticles and STING Agonists

• Published in: Advanced science Vol. 12; no. 3; pp. e2408539 - n/a
• Main Authors: Li, Yu‐an, Feng, Yi, Li, Wenjing, Zhang, Yuqin, Sun, Yanni, Wang, Shifeng, Curtiss, Roy, Shi, Huoying
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.01.2025; John Wiley and Sons Inc; Wiley
• Subjects: Adjuvants; Animals; Antigens; Bacteria; Biosynthesis; Cholera; Cytoplasm; Drug Delivery Systems - methods; Efficiency; Gram-positive bacteria; Humans; Immune system; Immunity (Disease); Localization; Membrane Proteins - agonists; Membranes; Mice; nanoparticle; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Peptides; Plasmids; Proteins; purely biological system; Salmonella; STING agonist; Toxins; Transmission electron microscopy; universal vaccine; Vaccines; Vaccines - immunology; nanoparticle; universal vaccine; STING agonist; purely biological system
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202408539

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. The PBNV system provides extensive antiviral effectiveness via the following mechanisms: (1) self‐assembly of diverse nanoparticles; (2) self‐catalyzed production of small‐molecule STING agonists; and (3) delivery vectors aimed at the cytosolic surveillance system. The system enhances the periplasmic targeting of cargos, hence improving the self‐assembly of nanoparticles. Furthermore, the system biosynthesizes STING agonists and demonstrates lymph node targeting in vivo.