M. Pizza et al., GENETICALLY DETOXIFIED DERIVATIVE OF HEAT-LABILE ESCHERICHIA-COLI ENTEROTOXIN INDUCES NEUTRALIZING ANTIBODIES AGAINST THE A-SUBUNIT, The Journal of experimental medicine, 180(6), 1994, pp. 2147-2153
Escherichia coli enterotoxin (LT) and the homologous cholera toxin (CT
) are A-B toxins that cause travelers' diarrhea and cholera, respectiv
ely. So far, experimental live and killed vaccines against these disea
ses have been developed using only the nontoxic B portion of these tox
ins. The enzymatically active A subunit has not been used because it i
s responsible for the toxicity and it is reported to induce a negligib
le titer of toxin neutralizing antibodies. We used site-directed mutag
enesis to inactivate the ADP-ribosyltransferase activity of the A subu
nit and obtained nontoxic derivatives of LT that elicited a good titer
of neutralizing antibodies recognizing the A subunit. These LT mutant
s and equivalent mutants of CT may be used to improve live and killed
vaccines against cholera and enterotoxinogenic E. coli.