缺乏ADP-核糖基转移酶活性的大肠杆菌不耐热毒素突变体可作为无毒的黏膜佐剂。
Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants.
作者信息
Douce G, Turcotte C, Cropley I, Roberts M, Pizza M, Domenghini M, Rappuoli R, Dougan G
机构信息
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, United Kingdom.
出版信息
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1644-8. doi: 10.1073/pnas.92.5.1644.
Abstract
A nontoxic mutant (LTK7) of the Escherichia coli heat-labile enterotoxin (LT) lacking ADP-ribosylating activity but retaining holotoxin formation was constructed. By using site-directed mutagenesis, the arginine at position 7 of the A subunit was replaced with lysine. This molecule, which was nontoxic in several assays, was able to bind to eukaryotic cells and acted as a mucosal adjuvant for co-administered proteins; BALB/c mice immunized intranasally with LTK7 and ovalbumin developed high levels of serum and local antibodies to ovalbumin and toxin. In addition, mice immunized intranasally with fragment C of tetanus toxin and LTK7 were protected against lethal challenge with tetanus toxin. Thus nontoxic mutants of heat-labile toxin can act as effective intranasal mucosal adjuvants.
摘要
构建了一种大肠杆菌不耐热肠毒素（LT）的无毒突变体（LTK7），其缺乏ADP核糖基化活性，但保留全毒素形成能力。通过定点诱变，将A亚基第7位的精氨酸替换为赖氨酸。该分子在多种检测中均无毒，能够结合真核细胞，并作为共同给药蛋白质的黏膜佐剂；用LTK7和卵清蛋白经鼻免疫的BALB/c小鼠产生了高水平的针对卵清蛋白和毒素的血清及局部抗体。此外，用破伤风毒素C片段和LTK7经鼻免疫的小鼠对破伤风毒素的致死性攻击具有抵抗力。因此，不耐热毒素的无毒突变体可作为有效的经鼻黏膜佐剂。
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Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants.缺乏ADP-核糖基转移酶活性的大肠杆菌不耐热毒素突变体可作为无毒的黏膜佐剂。
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1644-8. doi: 10.1073/pnas.92.5.1644.
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