Heat-labile enterotoxin of Escherichia coli and its site-directed mutant LTK63 enhance the proliferative and cytotoxic T-cell responses to intranasally co-immunized synthetic peptides

Abstract

The adjuvanticitity of heat-labile enterotoxin (LT) of Escherichia coli and its non-toxic mutant LTK63 was assessed and compared for intranasal immunization of synthetic peptides. Mice immunized intranasally with LT, or its mutant LTK63, generated strong systemic proliferative and cytotoxic T-cell responses to co-administered synthetic peptides. The wild LT toxin promoted higher peptide-specific proliferative and cytotoxic T-cell responses than the LTK63 mutant. Moreover, the wild-type LT toxin was shown to promote peptide-specific memory CTL responses which were detectable 1 year after intranasal priming. Both LT and LTK63 molecules were shown to be immunogenic, with serum antibody subclasses being predominantly IgG1 and to a lesser extent IgG2a. These findings demonstrate that cellular immune responses to small synthetic peptide antigens administered by the intranasal route can be potentiated with the use of mucosal adjuvants. Moreover, the ability of LT and LTK63 to promote both CD4+ and CD8+ T-cell responses will have relevance to the design and production of future mucosal vaccines.