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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic*
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Animals
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Bacterial Toxins / chemistry
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Bacterial Toxins / immunology*
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Bacterial Toxins / toxicity
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Enterotoxins / chemistry
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Enterotoxins / immunology*
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Enterotoxins / toxicity
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Escherichia coli
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Escherichia coli Proteins*
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Female
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Gastric Mucosa / immunology*
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Lung / immunology
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Mice
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Mice, Inbred BALB C
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Mutagenesis, Site-Directed
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Nasal Mucosa / immunology*
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Nose / immunology
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Ovalbumin / immunology
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Poly(ADP-ribose) Polymerases / chemistry
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Poly(ADP-ribose) Polymerases / genetics
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Poly(ADP-ribose) Polymerases / toxicity
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Structure-Activity Relationship
Substances
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Adjuvants, Immunologic
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Bacterial Toxins
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Enterotoxins
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Escherichia coli Proteins
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Ovalbumin
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heat-labile enterotoxin, E coli
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Poly(ADP-ribose) Polymerases