MUTANTS OF ESCHERICHIA-COLI HEAT-LABILE TOXIN LACKING ADP-RIBOSYLTRANSFERASE ACTIVITY ACT AS NONTOXIC, MUCOSAL ADJUVANTS

被引：236
作者：
DOUCE, G
TURCOTTE, C
CROPLEY, I
ROBERTS, M
PIZZA, M
DOMENGHINI, M
RAPPUOLI, R
DOUGAN, G
机构：
[1] UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,VACCINE RES UNIT,LONDON SW7 2AZ,ENGLAND
[2] IRIS,I-53100 SIENA,ITALY
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1995年 / 92卷 / 05期
关键词：
HEAT-LABILE ENTEROTOXIN; NONTOXIC MUTANT; TETANUS;
D O I：
10.1073/pnas.92.5.1644
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页码：1644 / 1648
页数：5
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