Is enzymatic activity required for adjuvanticity?
Despite several years of research and many reports on different immunomodulating properties it is still unclear which entity of CT is critical for adjuvanticity. Most investigators would agree that the adjuvant effect requires the intact holotoxin rather than the non-toxic B subunit, which has been found to possess only poor or no adjuvant ability.3 Whether the enzymatic activity of CTA1 is needed is currently an issue of intense investigations. Two different approaches have been attempted to advance our understanding in this field. The first approach uses site-directed mutagenesis of the CTA1 subunit to partly or completely disrupt the enzymatic activity of the holotoxin.37, 38, 39, 40, 41 This results in a holotoxin, AB5-heterohexamer, which retains the CTB-binding element. Several of these mutants have recently been found to exert adjuvant function although they lack ADP-ribosylating activity. As outlined in previous sections we chose a different approach by expressing the intact en
