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大肠杆菌不耐热肠毒素重组B亚基经鼻内免疫小鼠对灭活猪繁殖与呼吸综合征病毒抗原的Th1偏向性免疫佐剂作用

Th1-biased immunoadjuvant effect of the recombinant B subunit of an Escherichia coli heat-labile enterotoxin on an inactivated porcine reproductive and respiratory syndrome virus antigen via intranasal immunization in mice.

作者信息

Su Fei, Xu Lihua, Xue Yin, Li Junxing, Fu Yuan, Yu Bin, Wang Sai, Yuan Xiufang

机构信息

Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang 310002, China.

Zhejiang Center of Animal Disease Control, Hangzhou, Zhejiang 310020, China.

出版信息

J Vet Med Sci. 2019 Oct 24;81(10):1475-1484. doi: 10.1292/jvms.19-0057. Epub 2019 Sep 16.

DOI:10.1292/jvms.19-0057
PMID:31527353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6863725/
Abstract

Porcine reproductive and respiratory syndrome (PRRS) is one of the major swine diseases responsible for a significant challenge in the global swine industry. The current PRRS inactivated vaccine only confers limited protection against PRRSV. Thus, using an appropriate adjuvant via a suitable administration route may help improve vaccine efficacy. In this study, the recombinant B subunit of the Escherichia coli heat-labile enterotoxin rLTB, was highly expressed in Pichia pastoris, through high-density fermentation. rLTB intranasal adjuvant properties were evaluated on an inactivated PRRS antigen in mice. Compared to the group immunized with solely PRRS antigen, a dose of 50 µg rLTB remarkably raised antigen-specific IgA antibodies at mucosal sites, and increased serum IgG antibodies, preferentially the IgG2a and IgG2b subclasses. Further, rLTB induced increases in Th1- (IFN-γ and IL-12) and Th17 (IL-6) cytokine profiles, but had little effect on Th2 cytokine profiles (IL-4 and IL-10). Moreover, there were no overt toxicities associated with intranasal rLTB administration. Our data provide evidence that the rLTB produced by P. pastoris fermentation portrays low toxicity, and its intranasal adjuvant effect involves immune system modulation to a Th1 profile.

摘要

猪繁殖与呼吸综合征(PRRS)是全球养猪业面临重大挑战的主要猪病之一。目前的PRRS灭活疫苗对PRRS病毒的保护作用有限。因此,通过合适的给药途径使用合适的佐剂可能有助于提高疫苗效力。在本研究中,大肠杆菌不耐热肠毒素rLTB的重组B亚基在毕赤酵母中通过高密度发酵得到高效表达。在小鼠中对灭活的PRRS抗原评估了rLTB的鼻内佐剂特性。与仅用PRRS抗原免疫的组相比,50μg剂量的rLTB显著提高了粘膜部位的抗原特异性IgA抗体,并增加了血清IgG抗体,尤其是IgG2a和IgG2b亚类。此外,rLTB诱导Th1(IFN-γ和IL-12)和Th17(IL-6)细胞因子水平升高,但对Th2细胞因子水平(IL-4和IL-10)影响不大。而且,鼻内给予rLTB没有明显的毒性。我们的数据表明,毕赤酵母发酵产生的rLTB毒性低,其鼻内佐剂作用涉及将免疫系统调节为Th1型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/1c96d7a4d351/jvms-81-1475-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/7ecb361fe367/jvms-81-1475-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/740ccc747cf2/jvms-81-1475-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/954f02290e65/jvms-81-1475-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/0b83bc0b3382/jvms-81-1475-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/7eb8484720ff/jvms-81-1475-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/77c8e34c20bf/jvms-81-1475-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/1c96d7a4d351/jvms-81-1475-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/7ecb361fe367/jvms-81-1475-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/740ccc747cf2/jvms-81-1475-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/954f02290e65/jvms-81-1475-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/0b83bc0b3382/jvms-81-1475-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/7eb8484720ff/jvms-81-1475-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/77c8e34c20bf/jvms-81-1475-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a38/6863725/1c96d7a4d351/jvms-81-1475-g007.jpg

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