Adjuvant effect of non-toxic mutants of E. coli heat-labile enterotoxin following intranasal, oral and intravaginal immunization.
Cholera toxin and Escherichia coli heat-labile enterotoxin (LT) are known to be very effective mucosal adjuvants, but their toxicity limits their use in humans. We genetically detoxified LT by substituting single residues in the active site of the enzymatic A subunit and obtained mutant molecules that retain mucosal adjuvant activity but are devoid of toxicity. These mutant LT molecules induce mucosal and systemic responses to antigens delivered intranasally, orally and intravaginally in mice. Furthermore, mucosal immunization with these molecules confers protection against systemic challenge with tetanus toxin (TT) and mucosal challenge with Helicobacter pylori.
De Magistris
M T
MT
IRIS, Chiron Vaccines Immunobiological Research Institute, Siena, Italy.
Pizza
M
M
Douce
G
G
Ghiara
P
P
Dougan
G
G
Rappuoli
R
R
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000282:Administration, Intravaginal; D000284:Administration, Oral; D019943:Amino Acid Substitution; D000818:Animals; D001427:Bacterial Toxins / Q000009:adverse effects / Q000235:genetics* / Q000276:immunology*; D004768:Enterotoxins / Q000009:adverse effects / Q000235:genetics* / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics* / Q000276:immunology*; D029968:Escherichia coli Proteins; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D013744:Tetanus Toxin / Q000276:immunology
D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D013744:Tetanus Toxin; C027538:heat-labile enterotoxin, E coli