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

被引:23
作者
Bongat, Aileen F. G. [1 ]
Saksena, Rina [3 ]
Adamo, Roberto [1 ]
Fujimoto, Yukari [2 ]
Shiokawa, Zenyu [2 ]
Peterson, Dwight C. [3 ]
Fukase, Koichi [2 ]
Vann, Willie F. [3 ]
Kovac, Pavol [1 ]
机构
[1] NIDDK, LBC, NIH, Bethesda, MD 20892 USA
[2] Osaka Univ, Dept Chem, Grad Sch Sci, Osaka 5600043, Japan
[3] US FDA, OVRR, CBER, Lab Bacterial Toxins, Bethesda, MD 20892 USA
关键词
Conjugate vaccine; Vibrio cholerae; Adjuvant; Squaric acid; Tetanus toxin C fragment; VIBRIO-CHOLERAE O-1; SQUARIC ACID DIESTER; SEROTYPE OGAWA; C-13-NMR SPECTRA; DIETHYL SQUARATE; IMMUNE-RESPONSE; O-PS; PROTEIN; CARRIER; OLIGOSACCHARIDES;
D O I
10.1007/s10719-009-9259-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:69 / 77
页数:9
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