Combinations of protein polysaccharide conjugate vaccines for intranasal immunization.

The ability of 2 mutants of heat-labile Escherichia coli enterotoxin (LTK63 and LTR72) to enhance the immunogenicity of 2 protein polysaccharide conjugate vaccines, Neisseria meningitidis group C (MenC) and Haemophilus influenzae type B (Hib), both of which are conjugated to the nontoxic mutant of diphtheria toxin (CRM197), after intranasal (inl) immunization in mice was evaluated. In addition, the question of whether combining both vaccines in a single formulation with heat-labile E. coli enterotoxin mutants reduced the response to either vaccine was investigated. The results showed that potent serum antibody responses against MenC and Hib could be elicited by inl immunization in combination with the mucosal adjuvants. Moreover, IgA mucosal responses were induced only in animals immunized through the inl route. Finally, the coadministration of 2 conjugate vaccines simultaneously did not adversely affect the responses against either. These studies support the rationale for developing mucosal vaccines, based on combining protein polysaccharide conjugates with heat-labile E. coli enterotoxin mutants, for infants and young children.