Clostridium difficile recombinant toxin A repeating units as a carrier protein for conjugate vaccines: studies of pneumococcal type 14, Escherichia coli K1, and Shigella flexneri type 2a polysaccharides in mice.
Clostridium difficile recombinant toxin A repeating units as a carrier protein for conjugate vaccines: studies of pneumococcal type 14, Escherichia coli K1, and Shigella flexneri type 2a polysaccharides in mice.
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艰难梭菌重组毒素 A 重复单元作为结合疫苗的载体蛋白：对小鼠 14 型肺炎球菌、大肠杆菌 K1 和福氏志贺氏菌 2a 型多糖的研究。
DOI：
10.1128/iai.68.4.2161-2166.2000
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发表时间：
2000
影响因子：
3.1
通讯作者：
Schneerson,R
中科院分区：
文献类型：
--
作者：
Pavliakova,D;Moncrief,JS;Lyerly,DM;Schiffman,G;Bryla,DA;Robbins,JB;Schneerson,R
与天然蛋白质不同，来自艰难梭菌毒素A（CDTA）的无毒肽（天然毒素的重复单位，称为rARU）提供了一种抗原，可以共价结合到肺炎球菌14型，志贺氏菌2a型和大肠杆菌K1的表面多糖。这些多糖-蛋白质缀合物的产率通过用琥珀酸酐预先处理rARU而显著增加。通过临床相关剂量和免疫方案将用rARU或琥珀酰化（rARUsucc）制备的缀合物给予小鼠。所有缀合物引起高水平的血清免疫球蛋白G的多糖和CDTA。偶联物诱导的抗CDTA在体外具有中和活性，并保护用CDTA攻击的小鼠，与单独的rARU相似。因此，用琥珀酰化rARU制备的缀合物具有作为多糖的有效载体蛋白和预防由C引起的肠道疾病的潜力。很难
Unlike the native protein, a nontoxic peptide (repeating unit of the native toxin designated rARU) fromClostridium difficiletoxin A (CDTA) afforded an antigen that could be bound covalently to the surface polysaccharides of pneumococcus type 14,Shigella flexneritype 2a, andEscherichia coliK1. The yields of these polysaccharide-protein conjugates were significantly increased by prior treatment of rARU with succinic anhydride. Conjugates, prepared with rARU or succinylated (rARUsucc), were administered to mice by a clinically relevant dosage and immunization scheme. All conjugates elicited high levels of serum immunoglobulin G both to the polysaccharides and to CDTA. Conjugate-induced anti-CDTA had neutralizing activity in vitro and protected mice challenged with CDTA, similar to the rARU alone. Conjugates prepared with succinylated rARU, therefore, have potential for serving both as effective carrier proteins for polysaccharides and for preventing enteric disease caused byC. difficile.