ENHANCED IMMUNOGENICITY OF PROTEIN-DEXTRAN CONJUGATES .1. RAPID STIMULATION OF ENHANCED ANTIBODY-RESPONSES TO POORLY IMMUNOGENIC MOLECULES

In view of our observation that anti-immunoglobulin antibody conjugate d to high-molecular-weight dextran stimulates high levels of B-cell ac tivation (Brunswick et al. J. Immunol. 1989, 143, 1239), we coupled T cell-dependent antigens to dextran. When mice were immunized, in the a bsence of adjuvant, with a BSA-dextran conjugate (BSA-dex), a persiste nt, high-titre anti-BSA IgG1 response was induced. Titres were dose-de pendent and seen with as little as 10 mu g of conjugated protein. Anti -BSA titres were detected as early as day 7, usually peaked at about d ay 14 and persisted for at least 4 weeks. Anti-hapten antibodies were also elicited in mice that were immunized with haptenated BSA covalent ly bound to dextran, and secondary responses could be induced even aft er inoculation of the unconjugated protein. Covalent attachment of the protein to the polymer was necessary, and the response was specific, as coinjection of BSA-dex and an unrelated antigen, goat IgG, did not elicit detectable anti-goat antibodies. The immunogenic potential of t hese conjugates did not depend on the ability of the dextran carrier t o induce antibody, inasmuch as they stimulated high levels of anti-pro tein antibody in mice unresponsive to dextran. A minimum size dextran polymer was required for 2000 kDa but not of 70 kDa gave detectable an ti-BSA titres.