Rapid development of a subunit nano-vaccine against drug-resistant Pseudomonas aeruginosa with effective cross-protection

Abstract

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.