MUTANTS OF THE ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXIN WITH REDUCED ADP-RIBOSYLATION ACTIVITY OR NO ACTIVITY RETAIN THE IMMUNOGENIC PROPERTIES OF THE NATIVE HOLOTOXIN

The Escherichia coli heat-labile enterotoxin (LT) is a potent inducer of mucosal immune responses. In a previous study (L. DeHaan, W. R. Ver weij, M. Holtrop, E. Agsteribbe, and J. Wilschut, Vaccine 14:620-626, 1996), we have shown that efficient induction of an LTB-specific mucos al immune response by LT requires the presence of the LTA chain, sugge sting a possible role of the enzymatic activity of LTA in the inductio n of these responses. In the present study, we generated LT mutants,vi th altered ADP-ribosylation activities and evaluated their immunogenic ity upon intranasal administration to mice. The results demonstrate th at the mucosal immunogenicity of LT is not dependent on its ADP-ribosy lation activity.