LOCAL AND SYSTEMIC ANTIBODY-RESPONSES TO DEXTRAN-CHOLERA TOXIN B-SUBUNIT CONJUGATES

This study was designed to test Local and systemic immunity following mucosal immunization with a polysaccharide-protein conjugate, After pr eparing and characterizing dextran-cholera toxin B subunit (CTB) conju gates, we studied their immunogenicity in mice following systemic or m ucosal immunizations, Dextran was chosen as a model polysaccharide ant igen and conjugated via adipic acid dihydrazide and N-succinimidyl-3-( 2-pyridyldithio)propionate to CTB. Mice were immunized either subcutan eously, intranasally, or perorally three times, and cholera toxin was used as an adjuvant for the mucosal immunizations, Three conjugates wi th different molecular weights for dextran (40,000 and 76,000) or vary ing dextran/CTB molar ratios were tested, Peroral immunizations with a ll conjugates evoked local immunoglobulin A (IgA) antibody responses a gainst dextran in the small intestine, and intranasal immunizations di d the same in the lung. Intranasal immunizations also elicited serum a ntibody titers that were significantly higher than or equal to those a fter subcutaneous immunizations, Intranasal immunizations evoked serum IgG antidextran titers which were dependent on the dextran/CTB molar ratio and inversely related to the local IgA response, which was not t he case for subcutaneous immunizations, This is the first study of loc al and systemic immunity following mucosal immunization with a polysac charide protein conjugate, The results show that it is possible to evo ke a local as well as a systemic antibody response against a polysacch aride by conjugating it to CTB and using an appropriate route of immun ization.