Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants

G. Douce, C. Turcotte, I. Cropley, M. Roberts, M. Pizza, R. Rappuoli, G. Dougan

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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.

Original languageEnglish
Pages (from-to)1644-1648
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number5
DOIs
Publication statusPublished - 28 Feb 1995
Externally publishedYes

Keywords

  • Heat-labile enterotoxin
  • Nontoxic mutant
  • Tetanus

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