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一种展示 MERS-CoV 受体结合域的新型细菌样颗粒疫苗可在小鼠体内诱导特异性黏膜和系统免疫应答。

A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice.

机构信息

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.

出版信息

Viruses. 2019 Aug 29;11(9):799. doi: 10.3390/v11090799.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium ()-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP), RBD-linker-PA3 (RLP) and RBD-PA3 (RP)), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.

摘要

中东呼吸综合征冠状病毒(MERS-CoV)是一种新型冠状病毒,自 2012 年爆发以来,一直在人类中引发严重和致命的急性呼吸道疾病,引起了全球公众的恐惧。迫切需要开发预防和控制 MERS-CoV 感染的预防和治疗方法。在这项研究中,开发了一种展示 MERS-CoV 受体结合域(RBD)的细菌样颗粒(BLP)疫苗,并使用革兰氏阳性增强基质(GEM)颗粒作为基质,通过蛋白锚(PA)将 MERS-CoV RBD 外部结合。设计包括通过接头(RBD-接头-PA2(RLP)、RBD-接头-PA3(RLP)和 RBD-PA3(RP))连接的不同数量的溶菌酶基序(LysM)重复的 PA,融合蛋白中的三个 LysM 重复和一个接头增加了与 RBD 的结合活性。通过鼻腔内免疫接种 RLP-GEM 佐剂或不佐剂 GEL01 来测试针对特定的免疫反应。结果表明,GEL01 佐剂的 RLP-GEM 增加了小鼠模型中的全身体液、细胞和局部粘膜免疫反应,尤其是在肠道中。上述结果表明,MERS-CoV BLP 产品有可能开发成为一种有前途的粘膜候选疫苗,以预防 MERS-CoV 感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a363/6784119/a39df584004a/viruses-11-00799-g001.jpg

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