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.

引用

页码：1644 / 1648

页数：5

共 21 条

[1]

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[2]

CLARE JJ, 1991, BIOTECHNOLOGY, V9, P445

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