The antibody response to pneumococcal glycoconjugate (Pnc) was characterized by analyzing pneumococcal polysaccharide (PPS)– and protein carrier–specific IgG subclass profiles and their relationship. Mice were immunized intranasally (inl) or subcutaneously (sc) with Pnc with mutants of Escherichia coli heat-labile enterotoxin, LT-R72 and LT-K63, as mucosal adjuvants. Subcutaneous immunization with Pnc alone induced predominantly IgG1, whereas native PPS administered sc induced very low IgG titers that were exclusively of the IgG3 subclass. Compared with sc immunization with Pnc alone, inl immunization with Pnc and LT mutants induced significantly higher systemic IgG2a, IgG3, and IgA antibodies to both PPS and the carrier, whereas the IgG1 titers were comparable. There also was a significant correlation between PPS- and protein carrier–specific antibody responses for all IgG subclasses. This demonstrates that LT mutants can be used to both enhance and modulate the antibody response to the PS moiety of glycoconjugate vaccines