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. 1995 Feb 28;92(5):1644–1648. doi: 10.1073/pnas.92.5.1644

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

G Douce 1, C Turcotte 1, I Cropley 1, M Roberts 1, M Pizza 1, M Domenghini 1, R Rappuoli 1, G Dougan 1
PMCID: PMC42576  PMID: 7878032

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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