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Immunogenicity of a Dendrimer B2T Peptide Harboring a T-Cell Epitope From FMDV Non-structural Protein 3D

机译:来自FMDV非结构蛋白3D的树突式B2T肽的树突B2T肽的免疫原性

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Synthetic dendrimer peptides are a promising strategy to develop new FMD vaccines. A dendrimer peptide, termed B2T-3A, which harbors two copies of the major FMDV antigenic B-cell site [VP1 (140-158)], covalently linked to a heterotypic T-cell from the non-structural protein 3A [3A (21-35)], has been shown to protect pigs against viral challenge. Interestingly, the modular design of this dendrimer peptide allows modifications aimed at improving its immunogenicity, such as the replacement of the T-cell epitope moiety. Here, we report that a dendrimer peptide, B2T-3D, harboring a T-cell epitope from FMDV 3D protein [3D (56-70)], when inoculated in pigs, elicited consistent levels of neutralizing antibodies and high frequencies of IFN-γ-producing cells upon in vitro recall with the homologous dendrimers, both responses being similar to those evoked by B2T-3A. Lymphocytes from B2T-3A-immunized pigs were in vitro-stimulated by T-3A peptide and to a lesser extent by B-peptide, while those from B2T-3D- immunized animals preferentially recognized the T-3D peptide, suggesting that this epitope is a potent inducer of IFN-γ producing-cells. These results extend the repertoire of T-cell epitopes efficiently recognized by swine lymphocytes and open the possibility of using T-3D to enhance the immunogenicity and the protection conferred by B2T-dendrimers.
机译:合成树枝状蛋白肽是开发新型FMD疫苗的有希望的策略。一种Dendrimer肽,称为B2T-3A,其竖起来自主要FMDV抗原B细胞位点的两个拷贝[VP1(140-158)],与来自非结构蛋白3a的异质型T细胞共价连接[3a(21 -35)]已被证明可以保护猪免受病毒攻击。有趣的是,该树突肽的模块化设计允许旨在改善其免疫原性的修饰,例如替代T细胞表位部分。在这里,我们报道了一种树枝状聚合物肽,B2T-3D,来自FMDV 3D蛋白的T细胞表位[3D(56-70)],当接种在猪时,引发了一致的中和抗体和IFN-γ的高频率。 - 用同源树枝状过分器在体外召回体外召回时进行细胞,这两个反应都类似于B2T-3a引起的响应。通过T-3A肽的淋巴细胞由T-3A肽刺激,并通过B肽在较小程度上刺激,而来自B2T-3D-免疫动物的那些优先认识到T-3D肽,表明该表位是IFN-γ产生细胞的有效诱导剂。这些结果延伸了通过猪淋巴细胞有效识别的T细胞表位的曲目,并打开使用T-3D来增强免疫原性的可能性和B2T-树枝状大分子赋予的保护。

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