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携带猪δ冠状病毒S1基因的减毒鼠伤寒沙门氏菌的构建及免疫原性评价

Development and immunogenicity evaluation of attenuated Salmonella typhimurium delivering porcine Deltacoronavirus S1 gene.

作者信息

Yang Junpeng, Chen Rui, Sun Mengke, Yuan Rong, Xiao Ying Feng, Sun Ying, Zhou Guiping, Wen Yiping, Wang Yiping, Wu Rui, Zhao Qin, Du Senyan, Cao Sanjie, Huang Xiaobo

机构信息

Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

Chengdu Livestork and Poultry Genetic Resources Protection Center, China.

出版信息

Int J Biol Macromol. 2025 Feb;288:138615. doi: 10.1016/j.ijbiomac.2024.138615. Epub 2024 Dec 12.

DOI:10.1016/j.ijbiomac.2024.138615
PMID:39674474
Abstract

Porcine deltacoronavirus (PDCoV) is a swine enteropathogenic coronavirus that causes severe diarrhea in piglets, the development of novel vaccines is of great value in the prevention and control of PDCoV. Here, we selected attenuated Salmonella typhimurium SL7207 to deliver pVAX1-S1, resulting in the oral vaccine strain, SL7207 (pVAX1-S1). In immunized mice, SL7207 (pVAX1-S1) induced PDCoV-specific humoral IgG, IgA, neutralizing antibodies, mucosal sIgA, up-regulation of CD8 T cells, and increased levels of Th1 cytokines (IFN-γ and IL-2). In piglets, SL7207 (pVAX1-S1) induced high levels of PDCoV-specific humoral IgG and neutralizing antibodies but no detectable IgA, and only low levels of mucosal sIgA. SL7207 (pVAX1-S1) also promoted T cell differentiation into CD4 and CD8 T cells, and increased the expression level of IFN-γ and IL-4 in peripheral blood. Challenge experiments in piglets showed SL7207 (pVAX1-S1) alleviated diarrhea, decreased fecal virus load and intestinal lesions compared with control groups. In conclusion, this study systematically evaluated the immunogenicity and feasibility of attenuated Salmonella typhimurium delivering PDCoV S1 gene, which will provide helpful reference information for further exploration of novel PDCoV oral vaccine.

摘要

猪德尔塔冠状病毒(PDCoV)是一种引起仔猪严重腹泻的猪肠道致病性冠状病毒,开发新型疫苗对PDCoV的防控具有重要价值。在此,我们选择减毒鼠伤寒沙门氏菌SL7207来递送pVAX1-S1,从而获得口服疫苗株SL7207(pVAX1-S1)。在免疫小鼠中,SL7207(pVAX1-S1)诱导产生了PDCoV特异性体液IgG、IgA、中和抗体、黏膜sIgA,上调了CD8 T细胞水平,并提高了Th1细胞因子(IFN-γ和IL-2)的水平。在仔猪中,SL7207(pVAX1-S1)诱导产生了高水平的PDCoV特异性体液IgG和中和抗体,但未检测到IgA,且仅诱导产生了低水平的黏膜sIgA。SL7207(pVAX1-S1)还促进T细胞分化为CD4和CD8 T细胞,并提高了外周血中IFN-γ和IL-4的表达水平。仔猪攻毒实验表明,与对照组相比,SL7207(pVAX1-S1)减轻了腹泻,降低了粪便病毒载量和肠道病变。总之,本研究系统评估了减毒鼠伤寒沙门氏菌递送PDCoV S1基因的免疫原性和可行性,为进一步探索新型PDCoV口服疫苗提供了有益的参考信息。

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