Single-dose of hybrid eukaryotic-prokaryotic nanovesicles to drive a rapid and controllable immune response against Klebsiella pneumoniae induced nosocomial pneumonia
Single-dose of hybrid eukaryotic-prokaryotic nanovesicles to drive a rapid and controllable immune response against Klebsiella pneumoniae induced nosocomial pneumonia
复制标题
DOI：
10.1016/j.nantod.2023.102135
复制
发表时间：
2023-12-28
期刊：
影响因子：
17.4
通讯作者：
Liu，Gang
中科院分区：
文献类型：
--
作者：
Jiang，Lai;Ding，Linyu;Liu，Gang
肺炎克雷伯菌是引起急性肺炎的医院获得性感染的主要病原菌，具有耐药性、毒力和死亡率高的特点，目前尚无临床批准的疫苗制剂。在这里，我们设计了仿生混合膜囊泡（HMV），它由肺炎克雷伯菌的外膜囊泡和肺泡巨噬细胞的细胞膜囊泡组成。 HMV 通过气管内滴注来模拟吸入制剂的输送，其中免疫细胞可以在肺部快速动员，以促进病原体特异性免疫并建立局部粘膜免疫。在实验毒株 43,816 和临床毒株 7,29,088 的急性肺炎小鼠模型中，通过肺部进行 HMV 免疫提供了显着的保护作用，减少了深部组织中的菌落数量，提高了存活率，并减轻了急性炎症症状。正如预期的那样，HMV不仅保留了OMV的免疫原性，而且还有效降低了OMV诱导的过度免疫反应。总之，作为抗菌疫苗设计的概念验证，HMV是激活细菌特异性免疫的有效平台，可以快速有效地预防肺炎克雷伯菌引起的院内肺炎。
Klebsiella pneumoniaeis the main pathogen of hospital-acquired infections causing acute pneumonia, which is characterized by drug resistance, virulence and mortality, and for which there is no clinically approved vaccine formulations. Here, we designed biomimetic hybrid membrane vesicles (HMVs), which consist of outer membrane vesicles ofKlebsiella pneumoniaeand cell membrane vesicles of alveolar macrophages. The HMVs were administered via intratracheal instillation to mimic the delivery of an inhaled formulation, where immune cells could be rapidly mobilized in the lungs to promote pathogen-specific immunity and to establish local mucosal immunity. In a mouse model of acute pneumonia with experimental strain 43,816 and clinical strain 7,29,088, immunization of HMVs via the lungs provided significant protection, reduced the number of colonies in deep tissues, improved survival, and reduced symptoms of acute inflammation. As expected, HMVs not only retained the immunogenicity of OMVs, but also effectively reduced the excessive immune response induced by OMVs. In conclusion, as a proof-of-concept for the design of antibacterial vaccines, the HMVs is an effective platform for activating bacteria-specific immunity, which can rapidly and effectively protect against nosocomial pneumonia caused byKlebsiella pneumoniae.