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旋毛虫:携带 gp43 抗原衍生的 30 肽表位的减毒鼠伤寒沙门氏菌经鼻腔免疫可诱导 BALB/c 小鼠产生保护作用。

Trichinella spiralis: intranasal immunization with attenuated Salmonella enterica carrying a gp43 antigen-derived 30mer epitope elicits protection in BALB/c mice.

机构信息

Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología, Centro Médico Nacional La Raza, IMSS, Mexico City, Mexico.

出版信息

Exp Parasitol. 2011 Dec;129(4):393-401. doi: 10.1016/j.exppara.2011.08.013. Epub 2011 Aug 31.

Abstract

Trichinellosis is a public health problem and is considered an emergent/re-emergent disease in various countries. The etiological agent of trichinellosis is the nematode Trichinella, which infects domestic animals such as pigs and horses, as well as wild animals and humans. A veterinary vaccine could be an option to control the disease in domestic animals. Although several vaccine candidates have shown promising results, a vaccine against trichinellosis remains unavailable to date. Attenuated Salmonella strains are especially attractive live vectors because they elicit mucosal immunity, which is known to be important for the control of Trichinella spiralis infection at the intestinal level and can be administered by oral or intranasal routes. In this study, the autotransporter ShdA was used to display, on the surface of the Salmonella enterica serovar Typhimurium SL3261, the 210-239 amino acid epitope, (designated as Ag30) derived from the 43 kDa glycoprotein of T. spiralis muscle larvae. The fusion protein elicited antibodies in BALB/c mice that were able to recognize the native epitope on the surface of T. spiralis muscle larvae. Mice immunized by intranasal route with the recombinant Salmonella induced a protective immune response against the T. spiralis challenge, reducing by 61.83% the adult burden at day eight postinfection. This immune response was characterized by the induction of antigen-specific IgG1 and of IL-5 production. This study demonstrates the usefulness of Salmonella as a carrier of nematode epitopes providing a surface display system for intestinal parasite vaccine applications.

摘要

旋毛虫病是一个公共卫生问题,被认为是许多国家的新发/再发传染病。旋毛虫病的病原体是寄生在猪、马等家畜以及野生动物和人类体内的线虫旋毛虫。兽医疫苗可能是控制家畜疾病的一种选择。尽管有几种疫苗候选物显示出了有希望的结果,但到目前为止,还没有针对旋毛虫病的疫苗。减毒沙门氏菌菌株是特别有吸引力的活体载体,因为它们能引发黏膜免疫,而黏膜免疫被认为对控制肠道水平的旋毛虫感染很重要,并且可以通过口服或鼻腔途径进行给药。在这项研究中,自转运蛋白 ShdA 被用于在鼠伤寒沙门氏菌血清型 Typhimurium SL3261 的表面展示源自旋毛虫肌肉幼虫 43 kDa 糖蛋白的 210-239 个氨基酸表位(命名为 Ag30)。融合蛋白在 BALB/c 小鼠中引发了抗体反应,能够识别旋毛虫肌肉幼虫表面的天然表位。通过鼻腔途径用重组沙门氏菌免疫的小鼠对旋毛虫的挑战产生了保护性免疫反应,使感染后第 8 天的成虫负担减少了 61.83%。这种免疫反应的特征是诱导了抗原特异性 IgG1 和 IL-5 的产生。这项研究证明了沙门氏菌作为线虫表位载体的有用性,为肠道寄生虫疫苗的应用提供了一种表面展示系统。

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