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口服表达猪德尔塔冠状病毒S1蛋白的重组乳酸乳球菌诱导的黏膜免疫反应

Mucosal immune responses induced by oral administration of recombinant Lactococcus lactis expressing the S1 protein of PDCoV.

作者信息

Zhai Kaige, Zhang Zhongwang, Liu Xinsheng, Lv Jianliang, Zhang Liping, Li Jiahao, Ma Zhongyuan, Wang Yonglu, Guo Huichen, Zhang Yongguang, Pan Li

机构信息

State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.

出版信息

Virology. 2023 Jan;578:180-189. doi: 10.1016/j.virol.2022.12.010. Epub 2022 Dec 26.

Abstract

Porcine deltacoronavirus is an evolving coronavirus that primarily infects the intestine and may lead to intestinal disease in piglets. Up to now, no commercial vaccination is readily accessible to protect against the spread of PDCoV. Lactococcus lactis has been shown to have good immune efficacy and safety and can be used as a genetically engineered vaccine to deliver antigens. In this research, we utilized L. lactis NZ9000 to provide the S1 protein orally and improved the delivery efficiency by connecting the M cell targeting ligand Co1 with the S1 protein of PDCoV in tandem to obtain the recombinant protein S1-Co1. We successfully constructed two recombinant strains capable of expressing PDCoV-S1 and PDCoV-S1-Co1 proteins (i.e., L. lactis NZ9000-S1 and L. lactis NZ9000-S1-Co1), and their immunogenic capacity was evaluated in mice. Our study shows that Lactococcus is an advantageous bacterial live vector vaccine and is anticipated as a potential PDCoV vaccination option.

摘要

猪德尔塔冠状病毒是一种不断进化的冠状病毒,主要感染肠道,可能导致仔猪肠道疾病。到目前为止,尚无有效的商业疫苗可用于预防猪德尔塔冠状病毒的传播。乳酸乳球菌已被证明具有良好的免疫效果和安全性,可作为一种基因工程疫苗来递送抗原。在本研究中,我们利用乳酸乳球菌NZ9000口服提供S1蛋白,并通过将M细胞靶向配体Co1与猪德尔塔冠状病毒的S1蛋白串联连接来提高递送效率,从而获得重组蛋白S1-Co1。我们成功构建了两种能够表达猪德尔塔冠状病毒S1和猪德尔塔冠状病毒S1-Co1蛋白的重组菌株(即乳酸乳球菌NZ9000-S1和乳酸乳球菌NZ9000-S1-Co1),并在小鼠中评估了它们的免疫原性。我们的研究表明,乳酸乳球菌是一种有利的细菌活载体疫苗,有望成为预防猪德尔塔冠状病毒的潜在疫苗选择。

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