Multimeric bivalent immunogens from recombinant tetanus toxin HC fragment, synthetic hexasaccharides, and a glycopeptide adjuvant

Multimeric bivalent immunogens from recombinant tetanus toxin HC fragment, synthetic hexasaccharides, and a glycopeptide adjuvant
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DOI:
10.1007/s10719-009-9259-4
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发表时间:
2010-01-01
影响因子:
3
通讯作者:
Kovac, Pavol
Kovac, Pavol
中科院分区:
生物学4区
文献类型:
--
作者:
Bongat, Aileen F. G.;Saksena, Rina;Kovac, Pavol

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以重组破伤风毒素H-C片段(rTT-H-C)为载体,以小川型霍乱弧菌O:1的O-PS六糖片段为特征,结合稻叶型霍乱弧菌O:1的O-PS六糖片段或合成的二糖四肽肽聚糖片段作为佐剂,制备了多聚体双价免疫原。通过方酸化学实现缀合反应,并通过SELDI-TOF MS几乎真实的时间进行监测。以这种方式,我们可以制备具有可预测的碳水化合物-载体比的定义明确的免疫原,其分子量和每个糖的量可以独立地确定。制备这种新糖缀合物的能力为从合成碳水化合物制备用于细菌性疾病的缀合物疫苗开辟了前所未有的可能性。
Using recombinant tetanus toxin H-C fragment (rTT-H-C) as carrier, we prepared multimeric bivalent immunogens featuring the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Ogawa, in combination with either the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Inaba, or a synthetic disaccharide tetrapeptide peptidoglycan fragment as adjuvant. The conjugation reaction was effected by squaric acid chemistry and monitored in virtually real time by SELDI-TOF MS. In this way, we could prepare well-defined immunogens with predictable carbohydrate-carrier ratio, whose molecular mass and the amount of each saccharide attached could be independently determined. The ability to prepare such neoglycoconjugates opens unprecedented possibilities for preparation of conjugate vaccines for bacterial diseases from synthetic carbohydrates.