Characterization of the antibody response to pneumococcal glycoconjugates and the effect of heat-labile enterotoxin on IgG subclasses after intranasal immunization

The antibody response to pneumococcal glycoconjugate (Pnc) was characterize d by analyzing pneumococcal polysaccharide (PPS)- and protein carrier-speci fic IgG subclass profiles and their relationship. Mice were immunized intra nasally (inl) or subcutaneously (sc) with Pnc with mutants of Escherichia c oli heat-labile enterotoxin, LT-R72 and LT-K63, as mucosal adjuvants. Subcu taneous immunization with Pnc alone induced predominantly IgG1, whereas nat ive PPS administered sc induced very low IgG titers that were exclusively o f the IgG3 subclass. Compared with sc immunization with Pnc alone, inl immu nization with Pnc and LT mutants induced significantly higher systemic IgG2 a, IgG3, and IgA antibodies to both PPS and the carrier, whereas the IgG1 t iters were comparable. There also was a significant correlation between PPS - and protein carrier-specific antibody responses for all IgG subclasses. T his demonstrates that LT mutants can be used to both enhance and modulate t he antibody response to the PS moiety of glycoconjugate vaccines.