Lipid-coated nanoparticles enhance the delivery of bacterial virulence factors as a potent toxoid vaccine platform against bacterial infections

作者：Deli Zhuge, Yingnan Xiao, Yunxuan Huang, Yutong Zhong, Xueying Sun, Jing Wu, Shuangshuang Liu, Hui Liang, Weian Mao, Yang Yuan, Yijing Lin, Haonan Wang, Xuewei Yang, Xufei Zhang, Wenjie Sun, Caixia Liu, Ying‐Zheng Zhao, Mengchun Chen, Yijie Chen · 发表于：Cell Reports · 年份：2025 · DOI：10.1016/j.celrep.2025.115786 · 被引用次数：1 · 研究领域：RNA Interference and Gene Delivery、Lipid Membrane Structure and Behavior、Bacteriophages and microbial interactions

Antivirulence vaccination represents a promising strategy for infection prevention, but achieving both safety and efficacy in toxoid vaccine preparation remains a challenge. Cell membrane-based nanotoxoids offer a safe delivery platform for bacterial virulence factors in antivirulence vaccination, but limited absorption capacity hampers their efficacy. Here, we develop a lipid-based toxoid vaccine platform, PSV-CNP, comprising a CpG-loaded polymeric core coated with phosphatidylcholine/sphingomyelin (PS) liposomes enriched with bacterial virulence factors. By enhancing virulence factor absorption, PSV-CNP elicits robust humoral immunity. In mice, it provides long-lasting protection against methicillin-resistant Staphylococcus aureus (MRSA) and clinically isolated S. aureus (CI-SA), even under immunosuppression. In Bama pigs, PSV-CNP induces strong immune responses and prevents MRSA and CI-SA invasion. Furthermore, PS-liposomes efficiently absorb virulence factors from Pseudomonas aeruginosa (PA), conferring protection against PA infections. This study establishes PS-coated nanoparticles as a broadly applicable, safe, and effective antivirulence toxoid vaccine platform.