Cholera Toxin and its Subunits as Potential Oral Adjuvants

Abstract

Cholera toxin (CT) is a protein produced by Vibrio cholerae whose effect on the intestinal epithelial cells is responsible for the copious fluid secretion seen in clinical cholera. Because of this, the biology, immunology, and biochemistry of this molecule have been extensively characterized (Holmgren 1981; van Heyningen 1982). The molecular structure of CT is known and the genes encoding it have been isolated and sequenced (Mekalanos et al. 1983; Lockman and Kaper 1983). CT has two subunits, a 28,000 kD A subunit that has ADP-ribosylating enzymatic activity and an 11,500 kD B or binding subunit which exists as a pentamer in the holotoxin. The receptor molecule for CT is known to be GM1 ganglioside, a constituent of the cell surface membrane of virtually all nucleated cells. The A subunit can be further subdivided into A1 and A2 components which are encoded in the same gene segment and are linked by a disulfide bond. It is the hydrophobic A1 subunit that appears to insert into the membrane and mediate the activation of the adenylate cyclase enzyme.