As a highly contagious opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa) is one of the main causes of healthcare-associated infections. The drug-resistant nature of P. aeruginosa can render antibiotic treatments ineffective, leading to a high morbidity and mortality. Higher specificity and reduced toxicity are features of immunotherapy, which can generate robust immune responses and preserve long-term immunological memory to completely eradicate infections. In this study, we developed a type of P. aeruginosa vaccine based on a metal–organic framework. Specifically, MIL-101-Al nanoparticles were synthesized to encapsulate antigens derived from the bacterial lysate (BL) of PAO1, a drug-resistant P. aeruginosa, and the adjuvant unmethylated cytosine-phosphate-guanine oligonucleotide (CpG), which were then modified with palmitic acid (PAA) to obtain MIL-BC@PAA. The stability and biocompatibility were significantly increased by capping with PAA. Moreover, MIL-BC@PAA showed significantly enhanced uptake by antigen presenting cells (APCs), and promoted their maturation. Importantly, immunity studies revealed the greatly elicited antigen-specific humoral and cellular responses, and a protection rate of about 70% was observed in P. aeruginosa-challenged mice. Overall, these results demonstrate the promising potential of MIL-BC@PAA as an ideal nanovaccine for P. aeruginosa vaccination.

中文翻译：

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棕榈酸封端的 MIL-101-Al 作为纳米佐剂，可增强针对铜绿假单胞菌的免疫反应

作为一种高度传染性的机会性病原体，铜绿假单胞菌（P. aeruginosa）是医疗保健相关感染的主要原因之一。P的耐药性。铜绿假单胞菌可使抗生素治疗无效，导致高发病率和死亡率。免疫治疗的特点是特异性较高、毒性较小，可以产生强大的免疫反应，并保留长期的免疫记忆，从而彻底根除感染。在这项研究中，我们开发了一种基于金属有机框架的铜绿假单胞菌疫苗。具体来说，合成了 MIL-101-Al 纳米颗粒来封装源自 PAO1（一种耐药假单胞菌）细菌裂解物 (BL) 的抗原。铜绿假单胞菌和佐剂未甲基化胞嘧啶-磷酸-鸟嘌呤寡核苷酸（CpG），然后用棕榈酸（PAA）修饰以获得MIL-BC@PAA。 PAA 封端显着提高了稳定性和生物相容性。此外，MIL-BC@PAA 显着增强了抗原呈递细胞 (APC) 的摄取，并促进其成熟。重要的是，免疫研究表明，在P .铜绿假单胞菌攻击的小鼠。总的来说，这些结果证明了 MIL-BC@PAA 作为理想的疟原虫纳米疫苗的巨大潜力。接种铜绿假单胞菌疫苗。