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Oral vaccination with attenuated Salmonella encoding the Trichinella spiralis 43-kDa protein elicits protective immunity in BALB/c mice
Acta Tropica ( IF 2.7 ) Pub Date : 2021-07-28 , DOI: 10.1016/j.actatropica.2021.106071
Nan Wang 1 , Jun-Yao Wang 1 , Tian-Xu Pan 1 , Yan-Long Jiang 1 , Hai-Bin Huang 1 , Wen-Tao Yang 1 , Chun-Wei Shi 1 , Jian-Zhong Wang 1 , Dan Wang 1 , Dan-Dan Zhao 1 , Li-Min Sun 1 , Gui-Lian Yang 1 , Chun-Feng Wang 1
Affiliation  

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.



中文翻译:

用编码旋毛虫 43-kDa 蛋白的减毒沙门氏菌口服疫苗接种在 BALB/c 小鼠中引发保护性免疫

迫切需要一种针对旋毛虫感染的疫苗来阻止其从家畜到人类的传播。然而,目前没有针对螺旋线虫的疫苗可用。我们之前的研究表明,使用肌肉幼虫 (ML) 的排泄-分泌 (ES) 蛋白中存在的 43-kDa 糖蛋白作为肌内 DNA 疫苗可对螺旋线虫感染产生 52.1% 的保护率。减毒沙门氏菌菌株具有引发粘膜免疫的优势,这对于控制肠道阶段螺旋线虫感染很重要,可以通过口服或鼻内途径作为疫苗提供。因此,在本研究中,完整的 43-kDa 糖蛋白(旋毛虫的Ts 43)序列克隆到载体pYA3681中,将重组质粒pYA3681- Ts 43转化到鼠伤寒沙门氏菌减毒菌株χ11802中。结果表明,小鼠口服携带重组质粒 pYA3681- Ts 43 的减毒沙门氏菌疫苗接种后,局部肠粘膜 sIgA 和血清 IgG 抗体反应明显升高。流式细胞术结果显示CD4 + T细胞和分泌的IFN-γ、IL-4和IL-17A在CD4 +接种组的脾脏和肠系膜淋巴结 (MLN) 淋巴细胞中的 T 细胞显着增加。此外,在免疫组的血清中还观察到 IFN-γ、IL-4 和 IL-17A 细胞因子水平升高。免疫组的上述免疫反应结果表明本研究引发了保护性免疫。最后,接种疫苗的小鼠在感染旋毛虫后 ML 负担显着降低了 45.9% 。该研究表明,由减毒沙门氏菌提供的Ts 43口服疫苗接种引发了局部和全身并发 Th1/Th2/Th17 免疫反应,并提供了对螺旋线虫的部分保护BALB/c 小鼠的感染。这是预防和控制旋毛虫病的前瞻性策略。

更新日期:2021-08-04
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