A genetically detoxified derivative of heat-labile Escherichia coli enterotoxin induces neutralizing antibodies against the A subunit.
Escherichia coli enterotoxin (LT) and the homologous cholera toxin (CT) are A-B toxins that cause travelers' diarrhea and cholera, respectively. So far, experimental live and killed vaccines against these diseases have been developed using only the nontoxic B portion of these toxins. The enzymatically active A subunit has not been used because it is responsible for the toxicity and it is reported to induce a negligible titer of toxin neutralizing antibodies. We used site-directed mutagenesis to inactivate the ADP-ribosyltransferase activity of the A subunit and obtained nontoxic derivatives of LT that elicited a good titer of neutralizing antibodies recognizing the A subunit. These LT mutants and equivalent mutants of CT may be used to improve live and killed vaccines against cholera and enterotoxinogenic E. coli.
Pizza
M
M
Immunobiological Research Institute Siena (IRIS), Italy.
Fontana
M R
MR
Giuliani
M M
MM
Domenighini
M
M
Magagnoli
C
C
Giannelli
V
V
Nucci
D
D
Hol
W
W
Manetti
R
R
Rappuoli
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000276:immunology* / Q000633:toxicity; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D003062:Codon; D004768:Enterotoxins / Q000096:biosynthesis / Q000276:immunology* / Q000633:toxicity; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology*; D029968:Escherichia coli Proteins; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D009838:Oligodeoxyribonucleotides; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D011817:Rabbits / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology / Q000633:toxicity; D017386:Sequence Homology, Amino Acid
D000906:Antibodies; D001427:Bacterial Toxins; D003062:Codon; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; C027538:heat-labile enterotoxin, E coli; D011065:Poly(ADP-ribose) Polymerases