Infection resulting from carbapenem-resistant Klebsiella pneumoniae (CRKP) is an intractable clinical problem. Outer membrane vesicles (OMVs) from CRKP are believed to be potential vaccine candidates. However, their immune response remains elusive due to low structural stability and poor size homogeneity. In this study, hollow OMVs were reinforced internally by size-controlled BSA nanoparticles to obtain uniform and stable vaccines through hydrophobic interaction. The result showed that the BSA-OMV nanoparticles (BN-OMVs) were homogenous with a size around 100 nm and exhibited a core-shell structure. Remarkably, subcutaneous BN-OMVs vaccination mediated significantly higher CRKP specific antibody titers. The survival rate of the mice infected with a lethal dose of CRKP was increased significantly after BN-OMV immunization. The adoptive transfer experiment demonstrated that the protective effect of BN-OMVs was dependent on humoral and cellular immunity. This study demonstrated that the structure optimization improved the immune efficacy of OMVs for vaccine development against CRKP.

中文翻译：

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纳米颗粒增强的细菌外膜囊泡可有效预防对碳青霉烯耐药的肺炎克雷伯菌的致命感染。

由耐碳青霉烯类的肺炎克雷伯菌（CRKP）引起的感染是一个棘手的临床问题。据信，来自CRKP的外膜囊泡（OMV）是潜在的疫苗候选物。然而，由于低的结构稳定性和较差的尺寸均一性，它们的免疫应答仍然难以捉摸。在这项研究中，空心OMV通过尺寸控制的BSA纳米颗粒在内部进行增强，从而通过疏水相互作用获得均匀稳定的疫苗。结果表明，BSA-OMV纳米颗粒（BN-OMV）是均质的，尺寸约为100 nm，并显示出核-壳结构。值得注意的是，皮下注射BN-OMV介导的CRKP特异性抗体滴度明显更高。BN-OMV免疫后，致死剂量的CRKP感染的小鼠的存活率显着提高。过继转移实验表明，BN-OMVs的保护作用取决于体液和细胞免疫。这项研究表明，结构优化提高了OMV对CRKP疫苗开发的免疫效力。