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口服减毒沙门氏菌疫苗表达大肠杆菌 O157:H7 紧密素 γ可在小鼠中引发系统和黏膜体液免疫。

Oral immunization with attenuated Salmonella vaccine expressing Escherichia coli O157:H7 intimin gamma triggers both systemic and mucosal humoral immunity in mice.

机构信息

Department of Genetics, Evolution and Bioagents, Institute of Biology, Campinas State University, Campinas, SP, Brazil.

出版信息

Microbiol Immunol. 2012 Aug;56(8):513-22. doi: 10.1111/j.1348-0421.2012.00477.x.

Abstract

Human infections with EHEC such as O157:H7 have been a great concern for worldwide food-industry surveillance. This pathogen is commonly associated with bloody diarrhea that can evolve to the life-threatening hemolytic uremic syndrome. Animals are the natural reservoir where this pathogen remains asymptomatically, in steps of ingestion and colonization of the bowel. The bacterium is shed in the feces, contaminating the surroundings, including water and food that are directed for human consumption. A major player in this colonization process is intimin, an outer membrane adhesion molecule encoded by the E. coli attachment and effacement (eae) gene that has been shown to be essential for intimate bacterial attachment to eukaryotic host cells. In an attempt to reduce the colonization of animal reservoirs with EHEC O157:H7, we designed a vaccine model to induce an immune response against intimin gamma. The model is based on its recombinant expression in attenuated Salmonella, used as a suitable vaccine vector because of its recognized ability to deliver recombinant antigens and to elicit all forms of immunity: mucosal, systemic, and humoral responses. To test this model, mice were orally immunized with a S. enterica serovar Typhimurium strain carrying the pYA3137eaeA vector, and challenged with E. coli O157:H7. Here we show that immunization induced the production of high levels of specific IgG and IgA antibodies and promoted reduction in the fecal shedding of EHEC after challenge. The live recombinant vaccine reported herein may contribute to the efforts of reducing animal intestinal mucosa colonization.

摘要

人类感染肠出血性大肠杆菌(EHEC),如 O157:H7,一直是全球食品行业监测的重点。这种病原体通常与血性腹泻有关,可能会发展为危及生命的溶血性尿毒综合征。动物是这种病原体的自然宿主,它在摄入和定植肠道的过程中处于无症状状态。细菌会从粪便中排出,污染周围环境,包括用于人类食用的水和食物。在这个定植过程中,一个主要的参与者是紧密素,这是一种由大肠杆菌附着和消除(eae)基因编码的外膜粘附分子,它被证明对细菌与真核宿主细胞的紧密附着是必不可少的。为了减少动物宿主中 EHEC O157:H7 的定植,我们设计了一种疫苗模型来诱导针对紧密素γ的免疫反应。该模型基于其在减毒沙门氏菌中的重组表达,沙门氏菌被用作合适的疫苗载体,因为它具有公认的递送重组抗原的能力,并能引发所有形式的免疫反应:黏膜、系统和体液反应。为了测试该模型,我们用携带 pYA3137eaeA 载体的鼠伤寒沙门氏菌 Typhimurium 菌株对小鼠进行口服免疫,并对其进行 E. coli O157:H7 挑战。在这里,我们证明免疫诱导了高水平的特异性 IgG 和 IgA 抗体的产生,并促进了挑战后 EHEC 粪便脱落的减少。本文报道的活重组疫苗可能有助于减少动物肠道黏膜定植的努力。

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