Immune modulation by the cholera-like enterotoxin B-subunits: from adjuvant to immunotherapeutic

Cholera toxin (Ctx) and its close relative, Escherichia coli heat-labile enterotoxin (Etx) have long been established as potent mucosal and systemic adjuvants. Problems arising from their inherent toxicity have, however, precluded human use. Here we describe findings which demonstrate that contrary to the established dogma the non-toxic B-subunit of Etx (EtxB) is a highly potent mucosal adjuvant capable of potentiating protective immunity to viral infection. The mechanisms which underlie this activity arise from an ability to trigger specific signaling processes in lymphocyte populations which modulate differentially their activation, differentiation and survival. The elucidation of these properties has led to the further use of EtxB as an agent capable of preventing the establishment of autoimmune diseases. The basis for these activities and their potential applicability to human therapies are discussed.