Enhancing antibacterial immunotherapy for bacterial pneumonia via nanovaccines coated with outer membrane vesicles
Enhancing antibacterial immunotherapy for bacterial pneumonia via nanovaccines coated with outer membrane vesicles
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DOI：
10.1016/j.cej.2022.135040
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发表时间：
2022-02
影响因子：
15.1
通讯作者：
Yang Wu;Guiyun Deng;Zhiyong Song;Kai Zhang;Jiamin Deng;Kai Jiang;Heyou Han
中科院分区：
文献类型：
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作者：
Yang Wu;Guiyun Deng;Zhiyong Song;Kai Zhang;Jiamin Deng;Kai Jiang;Heyou Han
耐药微生物感染的增加和新抗生素类别批准数量的减少使得工程生物制剂难以用于传统疗法。在这里，我们报道了一种包裹在细菌外膜囊泡（OMVs）中的纳米疫苗，以增强细菌性肺炎的抗菌免疫治疗。以铜绿假单胞菌为模型病原体，以不可复制的细菌OMV为抗原，LPS为佐剂，成功合成LPS@DMON@OMV纳米疫苗。当皮下注射时，疫苗诱导免疫小鼠淋巴结中的树突状细胞（dc）快速激活和成熟。纳米疫苗刺激的特异性抗体滴度比游离OMV刺激的特异性抗体滴度高180倍，并且还可以刺激产生更多的毒性T细胞来消灭体内的细菌。此外，纳米疫苗还能刺激机体形成免疫记忆。体内的特异性抗体和记忆T细胞可以保留长达三个月，这可以防止细菌感染的风险。这些结果表明，利用天然细菌膜包封合成纳米颗粒在设计有效的抗菌疫苗方面具有广阔的前景。
The increase in drug-resistant microbial infections and the reduction in the number of approvals for new antibiotic categories make engineered biological agents difficult to use in traditional therapies. Here, we reported a nanovaccine encapsulated in the bacterial outer membrane vesicles (OMVs) to enhance the antibacterial immunotherapy of bacterial pneumonia. UsingPseudomonas aeruginosaas a model pathogen, we successfully synthesized the LPS@DMON@OMV nanovaccine using the non-replicable bacterial OMV as the antigen and LPS as the adjuvant. When injected subcutaneously, the vaccine induced rapid activation and maturation of dendritic cells (DCs) in the lymph nodes of immunized mice. The specific antibody titer stimulated by nanovaccine was 180 times higher than that stimulated by free OMV, and it can also stimulate the generation of more toxic T cells to eliminate bacteria in the body. In addition, the nanovaccine can also stimulate the body to form immune memory. The specific antibodies and memory T cells in the body can be retained for up to three months, which can prevent the risk of bacterial infection. These results indicate that the use of natural bacterial membranes to encapsulate synthetic nanoparticles has great prospects in the design of effective antibacterial vaccines.