Andrew Lees - Enhanced immunogenicity of protein-dextran conjugates: I. Rapid stimulation of enhanced antibody responses to poorly immunogenic molecules

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  Vaccine 12:1160, 1993



  In view of our observation that anti-immunoglobulin antibody   conjugated to high-molecular-weight dextran stimulates high   levels of B-cell activation (Brunswick et al. J. Immunol. 1989,   143, 1239), we coupled T cell-dependent antigens to dextran. When   mice were immunized, in the absence of adjuvant, with a   BSA-dextran conjugate (BSA-dex), a persistent, high-titre   anti-BSA IgG1 response was induced. Titres were dose-dependent   and seen with as little as 10 micrograms of conjugated protein.   Anti-BSA titres were detected as early as day 7, usually peaked   at about day 14 and persisted for at least 4 weeks. Anti-hapten   antibodies were also elicited in mice that were immunized with   haptenated BSA covalently bound to dextran, and secondary   responses could be induced even after 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 these conjugates did not depend on the ability of   the dextran carrier to induce antibody, inasmuch as they   stimulated high levels of anti-protein antibody in mice   unresponsive to dextran. A minimum size dextran polymer was   required for enhanced immunogenicity as conjugates of BSA with   dextran of molecular mass 500 or 2000 kDa but not of 70 kDa gave   detectable anti-BSA titres.

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