Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity.
Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity.
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DOI：
10.1038/emm.2015.59
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发表时间：
2015-09-11
影响因子：
12.8
通讯作者：
Jeon SG
中科院分区：
文献类型：
--
作者：
Lee WH;Choi HI;Hong SW;Kim KS;Gho YS;Jeon SG
耐多药肺炎克雷伯氏菌的出现突显了制定预防措施以改善克雷伯氏菌感染的必要性。细菌来源的胞外囊泡(EVS)是一种富含外膜蛋白的球形纳米蛋白脂。革兰氏阴性细菌衍生的EV已被用作无生命的复杂疫苗。在本研究中，我们评估了肺炎克雷伯菌来源的EVS是否对细菌诱导的致死性具有保护作用。从体外细菌培养上清液中分离的肺炎克雷伯菌来源的EV可诱导天然免疫，包括上调共刺激分子的表达和促炎介质的产生。通过腹膜途径接种EV疫苗可激发EV反应性抗体和产生干扰素-伽马的T细胞反应。用EVS接种了三次疫苗，防止了细菌诱导的死亡。经血清和脾细胞过继转移证实，EV疫苗的保护作用依赖于体液免疫和细胞免疫。综上所述，这些发现表明肺炎克雷伯菌衍生的EV是一种新的肺炎克雷伯菌感染疫苗候选。
The emergence of multidrug-resistant Klebsiella pneumoniae highlights the need to develop preventive measures to ameliorate Klebsiella infections. Bacteria-derived extracellular vesicles (EVs) are spherical nanometer-sized proteolipids enriched with outer membrane proteins. Gram-negative bacteria-derived EVs have gained interest for use as nonliving complex vaccines. In the present study, we evaluated whether K. pneumoniae-derived EVs confer protection against bacteria-induced lethality. K. pneumoniae-derived EVs isolated from in vitro bacterial culture supernatants induced innate immunity, including the upregulation of co-stimulatory molecule expression and proinflammatory mediator production. EV vaccination via the intraperitoneal route elicited EV-reactive antibodies and interferon-gamma-producing T-cell responses. Three vaccinations with the EVs prevented bacteria-induced lethality. As verified by sera and splenocytes adoptive transfer, the protective effect of EV vaccination was dependent on both humoral and cellular immunity. Taken together, these findings suggest that K. pneumoniae-derived EVs are a novel vaccine candidate against K. pneumoniae infections.