A NOVEL CONCEPT IN MUCOSAL ADJUVANTICITY - THE CTA1-DD ADJUVANT IS A B-CELL-TARGETED FUSION PROTEIN THAT INCORPORATES THE ENZYMATICALLY ACTIVE CHOLERA-TOXIN A1 SUBUNIT

A promising novel concept in mucosal adjuvant research is demonstrated here. The adjuvant and toxic effects of the cholera toxin (CT) have b een successfully separated in a gene fusion protein: CTA1-DD. This pro tein consists of the ADP-ribosylating Al subunit of CT Linked to a syn thetic analogue of protein A. The CTA1-DD protein was found to exert c omparable adjuvant activity to that of CT after systemic as well as mu cosal immunizations with soluble protein antigens, such as KLH or oval bumin (OVA). However, contrary to CT it was completely non-toxic. The CTA1-DD approach to the construction of a potential vaccine adjuvant i s unique and highly promising. Conceptually, the CTA1-DD fusion protei n demonstrates that: (i) contrary to CT the CTA1-DD is a highly target ed adjuvant, directed to B cells and possibly other antigen-presenting cells; (ii) it is possible to introduce ADP-ribosyltransferase activi ty into cells via an alternative pathway to the GM1 receptor pathway u sed by CTB; (iii) the adjuvant effect of CTA1-DD, and possibly also of CT, depend on the enzymatic activity; and (iv) one possible mechanism . shared by CT, that may explain the adjuvant effect of CTA1-DD is its ability to induce expression of the costimulatory molecule CD86 on B cells.