A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice
A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice
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DOI：
10.3390/v11090799
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发表时间：
2019-09-01
期刊：
影响因子：
4.7
通讯作者：
Xia, Xianzhu
中科院分区：
文献类型：
--
作者：
Li, Entao;Chi, Hang;Xia, Xianzhu
中东呼吸综合征冠状病毒(MERS-CoV)是一种新的冠状病毒，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，已引起全球公众的恐惧。为了预防和控制MERS冠状病毒感染，迫切需要开发预防和治疗药物。本研究以革兰氏阳性增强子基质(GEM)为底物，通过蛋白锚(PA)与MERS-CoV受体结合区(RBD)结合，构建了MERS-CoV受体结合域(RBD)细菌样颗粒(BLP)疫苗。设计包括由连接物(RBD-Linker-PA2(RLP2)、RBD-Linker-PA3(RLP3)和RBD-PA3(RP3))连接的PA中不同数量的溶素基序(LysM)重复，并且融合蛋白中的三个LysM重复和一个连接子增加了与RBD的结合活性。用含或不含GEL01佐剂的RLP3-GEM滴鼻免疫小鼠，检测其特异性免疫应答。结果表明，GEL01佐剂的RLP3-GEM可增强小鼠的体液免疫、细胞免疫和局部黏膜免疫应答，尤其是肠道免疫应答。以上结果表明，MERS-CoV BLP产品有可能发展成为一种有前景的黏膜候选疫苗，以保护MERS-CoV感染。
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 (Lactococcus lactis)-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 (RLP2), RBD-linker-PA3 (RLP3) and RBD-PA3 (RP3)), 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 RLP3-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP3-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.