Employing Escherichia coli-derived outer membrane vesicles as an antigen delivery platform elicits protective immunity against Acinetobacter baumannii infection.
Employing Escherichia coli-derived outer membrane vesicles as an antigen delivery platform elicits protective immunity against Acinetobacter baumannii infection.
复制标题
利用大肠杆菌来源的外膜囊泡作为抗原递送平台可引发针对鲍曼不动杆菌感染的保护性免疫
DOI：
10.1038/srep37242
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发表时间：
2016-11-16
影响因子：
4.6
通讯作者：
Ma Y
中科院分区：
文献类型：
--
作者：
Huang W;Wang S;Yao Y;Xia Y;Yang X;Li K;Sun P;Liu C;Sun W;Bai H;Chu X;Li Y;Ma Y
外膜囊泡（OMV）已被证明具有高度免疫原性，并在人类临床和动物模型中诱导针对细菌感染的免疫应答。我们试图研究工程化的OMV是否可以成为有效诱导特异性抗体应答的可行的抗原递送平台。本研究中，Omp 22（A. baumannii）在E. coli DH 5 α衍生的OMV（Omp 22-OMV）。Omp 22-OMV的形态特征与野生型OMV（wtOMV）的形态特征相似。用Omp 22-OMV免疫诱导高滴度的Omp 22特异性抗体。在小鼠脓毒症模型中，Omp 22-OMV免疫显著保护小鼠免受临床分离的A.鲍曼不动杆菌菌株，这通过小鼠的存活率增加、肺、脾、肝、肾和血液中的细菌负荷减少以及炎性细胞因子的血清水平抑制来证明。体外调理吞噬实验表明，Omp 22-OMV免疫小鼠获得的抗血清对临床分离株具有杀菌活性，且部分依赖于特异性抗体。这些结果有力地表明，工程化的OMV可以在表面上展示完整的异源蛋白（约22 kDa），并有效地诱导特异性抗体应答，因此OMV具有成为可行的疫苗平台的潜力。
Outer membrane vesicles (OMVs) have proven to be highly immunogenic and induced an immune response against bacterial infection in human clinics and animal models. We sought to investigate whether engineered OMVs can be a feasible antigen-delivery platform for efficiently inducing specific antibody responses. In this study, Omp22 (an outer membrane protein of A. baumannii) was displayed on E. coli DH5α-derived OMVs (Omp22-OMVs) using recombinant gene technology. The morphological features of Omp22-OMVs were similar to those of wild-type OMVs (wtOMVs). Immunization with Omp22-OMVs induced high titers of Omp22-specific antibodies. In a murine sepsis model, Omp22-OMV immunization significantly protected mice from lethal challenge with a clinically isolated A. baumannii strain, which was evidenced by the increased survival rate of the mice, the reduced bacterial burdens in the lung, spleen, liver, kidney, and blood, and the suppressed serum levels of inflammatory cytokines. In vitro opsonophagocytosis assays showed that antiserum collected from Omp22-OMV-immunized mice had bactericidal activity against clinical isolates, which was partly specific antibody-dependent. These results strongly indicated that engineered OMVs could display a whole heterologous protein (~22 kDa) on the surface and effectively induce specific antibody responses, and thus OMVs have the potential to be a feasible vaccine platform.