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Cell reports

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

Published:24 June 2025 DOI: 10.1016/j.celrep.2025.115786 PMID: 40482034
Deli Zhuge,?Yingnan Xiao,?Yunxuan Huang,?Yutong Zhong,?Xueying Sun,?Jing Wu,?Shuangshuang Liu,?Hui Liang,?Weian Mao,?Yuan Yang,?Yijing Lin,?Haonan Wang,?Xuewei Yang,?Xufei Zhang,?Wenjie Sun,?Caixia Liu,?Yingzheng Zhao,?Mengchun Chen,?Yijie Chen

Abstract

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.

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