Mutant Heat-Labile Entertoxins As Adjuvants for CTL Induction

Heat-labile enterotoxin (LT) from Escherichia coli and Cholera toxin (CT) from Vibro cholerae are known to be potent mucosal immunogens. These toxins have 80% sequence homology and a similar tertiary structure (1 ,4 ), and both elicit potent serum IgG and mucosal IgA responses (5 ,6 ). Moreover, both also serve as excellent adjuvants for coadministered antigens. However, they are toxic in their native state and both produce accumulation of intestinal fluid and watery diarrhea (7 ). LT is the cause of traveler’s diarrhea, whereas CT causes cholera. In order to make use of the adjuvanticity of these molecules but reduce their toxicity, several mutants have been generated by site-directed mutagenesis. Of these, there are two mutants of the enzymatic A subunit, LTK63 and LTR72, that maintain a high level of immunogenicity and have significant potential as adjuvants. This chapter will focus on the use of LTK63 and LTR72 as intramuscular and intranasal adjuvants for the induction of cytotoxic T lymphocytes (CTL) activity against coadministered protein immunogens.