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, 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.