口服减毒沙门氏菌疫苗免疫编码旋毛虫 43kDa 蛋白可诱导 BALB/c 小鼠保护性免疫。
Oral vaccination with attenuated Salmonella encoding the Trichinella spiralis 43-kDa protein elicits protective immunity in BALB/c mice.
机构信息
College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Key Laboratory of animal production and product quality safety of Ministry of Education, Jilin Agricultural University, Changchun, China.
College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Key Laboratory of animal production and product quality safety of Ministry of Education, Jilin Agricultural University, Changchun, China.
出版信息
Acta Trop. 2021 Oct;222:106071. doi: 10.1016/j.actatropica.2021.106071. Epub 2021 Jul 28.
A vaccine against Trichinella spiralis infection is urgently needed to interrupt its transmission from domestic animals to humans. However, no vaccine against T. spiralis is currently available. Our previous study demonstrated that the use of the 43-kDa glycoprotein present in excretory-secretory (ES) proteins of muscle larvae (ML) as an intramuscular DNA vaccine led to a 52.1% protection rate against T. spiralis infection. Attenuated Salmonella strains have the advantage of eliciting mucosal immunity, which is important for controlling T. spiralis infections at the intestinal stage and can be provided as vaccines via oral or intranasal routes. Therefore, in this study, complete 43-kDa glycoprotein (Ts43) sequences of T. spiralis were cloned into the vector pYA3681, and the recombinant plasmid pYA3681-Ts43 was transformed into the attenuated Salmonella typhimurium strain χ11802. The results showed that oral vaccination of mice with attenuated Salmonella carrying the recombinant plasmid pYA3681-Ts43 induced an evident elevation of the local intestinal mucosal sIgA and serum IgG antibody responses. The flow cytometry results showed that the percentages of CD4 T cells and secreted IFN-γ, IL-4, and IL-17A in CD4 T cells were significantly increased in the spleen and mesenteric lymph node (MLN) lymphocytes of the vaccinated groups. In addition, increased levels of the IFN-γ, IL-4, and IL-17A cytokines were also observed in the serum of the immunized groups. The above immune response results in the immunized groups demonstrated that protective immunity was elicited in this study. Finally, vaccinated mice demonstrated a significant 45.9% reduction in ML burden after infection with T. spiralis. This study demonstrated that oral vaccination with Ts43 delivered by attenuated Salmonella elicited local and systemic concurrent Th1/Th2/Th17 immune responses and provided partial protection against T. spiralis infection in BALB/c mice. This is a prospective strategy for the prevention and control of trichinellosis.
一种针对旋毛虫感染的疫苗对于从家畜到人类的传播至关重要。然而，目前尚无针对旋毛虫的疫苗。我们之前的研究表明，使用肌肉幼虫（ML）排泄-分泌（ES）蛋白中存在的 43-kDa 糖蛋白作为肌肉内 DNA 疫苗，可导致对旋毛虫感染的保护率达到 52.1%。减毒沙门氏菌菌株具有诱导黏膜免疫的优势，这对于控制肠道阶段的旋毛虫感染很重要，并且可以通过口服或鼻内途径提供作为疫苗。因此，在这项研究中，将完整的 43-kDa 糖蛋白（Ts43）序列克隆到载体 pYA3681 中，然后将重组质粒 pYA3681-Ts43 转化为减毒鼠伤寒沙门氏菌菌株 χ11802。结果表明，用携带重组质粒 pYA3681-Ts43 的减毒沙门氏菌口服接种小鼠可显著提高局部肠道黏膜 sIgA 和血清 IgG 抗体反应。流式细胞术结果显示，在接种组的脾脏和肠系膜淋巴结（MLN）淋巴细胞中，CD4 T 细胞的百分比以及 CD4 T 细胞中分泌的 IFN-γ、IL-4 和 IL-17A 均显著增加。此外，在免疫组的血清中也观察到 IFN-γ、IL-4 和 IL-17A 细胞因子水平的升高。免疫组的上述免疫反应结果表明，在本研究中诱导了保护性免疫。最后，感染旋毛虫后，接种疫苗的小鼠的 ML 负担显著降低了 45.9%。这项研究表明，用减毒沙门氏菌传递 Ts43 的口服接种可引起局部和全身同时的 Th1/Th2/Th17 免疫反应，并为 BALB/c 小鼠提供了对旋毛虫感染的部分保护。这是一种预防和控制旋毛虫病的有前途的策略。
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