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A novel linker methodology for the synthesis of tailored conjugate vaccines composed of complex carbohydrate antigens and specific T-H-cell peptide epitopes

机译:一种新颖的接头方法,用于合成由复杂的碳水化合物抗原和特定的T-H细胞肽表位组成的量身定制的偶联疫苗

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摘要

Pathogenic organisms or oncogenically transformed cells often express complex carbohydrate structures at their cell surface, which are viable targets for active immunotherapy. We describe here a novel, immunologically neutral, linker methodology for the efficient preparation of highly defined vaccine conjugates that combine complex saccharide antigens with specific T-H-cell peptide epitopes. This novel heterobifunctional approach was employed for the conjugation of a (1 -> 2)-beta-mannan trisaccharide from the pathogenic fungus Candida albicans as well as the carbohydrate portion of tumor-associated ganglioside GM(2) to a T-H-cell peptide epitope derived from the murine 60 kDa self heat-shock protein (hsp60). Moreover, the linkage chemistry has proven well suited for the synthesis of more complex target structures such as a biotinylated glycopeptide, a three component vaccine containing an immunostimulatory peptide epitope from interleukin-1 beta (IL-1 beta), and for the conjugation of complex carbohydrates to carrier proteins such as bovine serum albumin.
机译:致病生物或致癌转化细胞通常在其细胞表面表达复杂的碳水化合物结构,这是主动免疫疗法的可行目标。我们在这里描述了一种新型的,免疫中性的,用于高效制备结合复杂糖抗原与特定T-H细胞肽表位的高清晰度疫苗结合物的方法。这种新颖的异质双功能方法被用于从致病性真菌白色念珠菌以及与肿瘤相关的神经节苷脂GM(2)的碳水化合物部分到TH细胞肽表位的(1-> 2)-β-甘露聚糖三糖缀合。衍生自鼠类60 kDa自热激蛋白(hsp60)。此外,已证明连接化学非常适合于合成更复杂的靶标结构,例如生物素化的糖肽,包含来自白介素-1β(IL-1 beta)的免疫刺激性肽表位的三组分疫苗,以及复合物的缀合。碳水化合物与载体蛋白(例如牛血清白蛋白)结合。

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