Journal
NANO TODAY
Volume 43, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2022.101398
Keywords
Drug-resistant Pseudomonas aeruginosa; Nano-vaccine; Cross-protection; Comprehensive antigens; Cytosolic antigens; Membrane antigens
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Funding
- National Natural Science Foundation of China [81925036, 81872814]
- Key Research and Development Program of Science and Technology Department of Sichuan Province [2020YFS0570]
- Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System (CARS-SVDIP)
- Fundamental Research Funds for the Central Universities
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This study reports a facile strategy for the rapid development of a highly effective cross-protective Pseudomonas aeruginosa vaccine. By loading cytosolic antigens derived from bacterial lysates into mesoporous silica nanospheres and fusing membrane antigens onto the surface, the engineered nano-vaccines induced potent humoral and cellular immune responses and protected against different strains of Pseudomonas aeruginosa infection.
The complex antigen composition and limited selection of adjuvants restricted the development of Pseudomonas aeruginosa (P. aeruginosa) subunit vaccines. The evolvement of multiple serotypes of P. aeruginosa also challenges current vaccine candidates due to their poor cross-protection capacity. Herein, we first report a facile strategy to prepare comprehensive antigens loaded nano-vaccines for the rapid development of a P. aeruginosa vaccine with a highly effective cross-protection capacity. Namely, cytosolic antigens derived from bacterial lysates (BL) of PAO1, a drug-resistant P. aeruginosa, were loaded in the mesoporous silica nanospheres (MSNs), while membrane antigens derived from double-layered membrane vesicles (DMVs) of PAO1 were further fused on MSNs surface. The engineered MSN-BL@DMV showed a clear core-shell morphology, and it significantly promoted cellular internalization and maturation of dendritic cells without additional adjuvants. After subcutaneous vaccination, MSN-BL@DMV prepared from PAO1 efficiently migrated to lymph nodes, potently induced the humoral and cellular immune responses with exquisite specificity, and substantially protected mice from the challenge of PAO1 and another drug -resistant P. aeruginosa (PA-XN-1). In summary, the MSNs-based comprehensive antigen delivery system successfully protected mice from different strains of P. aeruginosa infection, providing new insights for treatment of other refractory pathogen infections. (c) 2022 Published by Elsevier Ltd.
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