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迈向猪带绦虫囊尾蚴病疫苗:一种由肥胖带绦虫和猪带绦虫共有的表位可保护小鼠抵御实验性囊尾蚴病。

Towards a Taenia solium cysticercosis vaccine: an epitope shared by Taenia crassiceps and Taenia solium protects mice against experimental cysticercosis.

作者信息

Toledo A, Larralde C, Fragoso G, Gevorkian G, Manoutcharian K, Hernández M, Acero G, Rosas G, López-Casillas F, Garfias C K, Vázquez R, Terrazas I, Sciutto E

机构信息

Department of Immunology, Instituto de Investigaciones Biomédicas, UNAM, México D.F. 04510, México.

出版信息

Infect Immun. 1999 May;67(5):2522-30. doi: 10.1128/IAI.67.5.2522-2530.1999.

Abstract

The Taenia crassiceps recombinant antigen KETc7 has been shown to be effective as a vaccine against experimental murine cysticercosis, a laboratory model used to test potentially promising molecules against porcine Taenia solium cysticercosis. Based on the deduced amino acid sequence of this proline-rich polypeptide, three fragments, GK-1, GK-2, and GK-3, were chemically synthesized in linear form. Of the three peptides, only GK-1 induced sterile protection against T. crassiceps cysticercosis in 40 to 70% of BALB/cAnN male mice. GK-1 is an 18-amino-acid peptide which contains at least one B-cell epitope, as demonstrated by its ability to induce an antibody response to the peptide and T. crassiceps antigen without need of a carrier protein. Immunofluorescence studies revealed that anti-GK1 antibodies strongly react with the native protein in the tegument of T. crassiceps and also with anatomical structures of T. solium eggs, oncospheres, cysticercus, and tapeworm. GK-1 also contains at least one T-cell epitope, capable of stimulating the proliferation of CD8(+) and to a lower extent CD4(+) T cells primed either with the free peptide or T. crassiceps total antigen. The supernatant of the stimulated cells contained high levels of gamma interferon and low levels of interleukin-4. Similar results were obtained with T cells tested for intracellular cytokine production, an indication of the peptide's capacity to induce an inflammatory response. The remarkable protection induced by GK-1 immunization, its physicochemical properties, and its presence in all developmental stages of T. solium point to this synthetic peptide as a strong candidate in the construction of a synthetic vaccine against T. solium pig cysticercosis.

摘要

肥胖带绦虫重组抗原KETc7已被证明作为一种疫苗,对实验性鼠囊尾蚴病有效,鼠囊尾蚴病是一种实验室模型,用于测试针对猪带绦虫囊尾蚴病可能有前景的分子。基于这种富含脯氨酸的多肽的推导氨基酸序列,化学合成了三个线性形式的片段,即GK-1、GK-2和GK-3。在这三种肽中,只有GK-1能在40%至70%的BALB/cAnN雄性小鼠中诱导对肥胖带绦虫囊尾蚴病的无菌保护。GK-1是一种18个氨基酸的肽,它含有至少一个B细胞表位,这可通过其在无需载体蛋白的情况下诱导针对该肽和肥胖带绦虫抗原的抗体反应的能力得以证明。免疫荧光研究表明,抗GK1抗体与肥胖带绦虫皮层中的天然蛋白以及猪带绦虫卵、六钩蚴、囊尾蚴和绦虫的解剖结构强烈反应。GK-1还含有至少一个T细胞表位,能够刺激用游离肽或肥胖带绦虫总抗原致敏的CD8(+)T细胞增殖,并在较低程度上刺激CD4(+)T细胞增殖。受刺激细胞的上清液中含有高水平的γ干扰素和低水平的白细胞介素-4。在用细胞内细胞因子产生进行测试的T细胞中也获得了类似结果,这表明该肽具有诱导炎症反应的能力。GK-1免疫诱导的显著保护作用、其理化性质以及它在猪带绦虫所有发育阶段的存在,表明这种合成肽是构建针对猪带绦虫囊尾蚴病的合成疫苗的有力候选物。

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