Open AccessMutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants.
Author(s) -
Gill Douce,
Claude Turcotte,
Ian Cropley,
Mark Roberts,
Mariagrazia Pizza,
M Domenghini,
Rino Rappuoli,
Gordon Dougan
Publication year - 1995
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.92.5.1644
Subject(s) - ovalbumin , heat labile enterotoxin , toxin , escherichia coli , mutant , microbiology and biotechnology , enterotoxin , diphtheria toxin , nasal administration , adjuvant , chemistry , mutagenesis , immunogenicity , antibody , biology , biochemistry , virology , antigen , immunology , gene
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.