title: Enhanced immunogenicity of protein-dextran conjugates: I. Rapid stimulation of enhanced antibody responses to poorly immunogenic molecules.
abstract: 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.
authors.affiliation: Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
authors.forename: A
authors.initials: A
authors.lastname: Lees
authors.forename: F
authors.initials: F
authors.lastname: Finkelman
authors.forename: J K
authors.initials: JK
authors.lastname: Inman
authors.forename: K
authors.initials: K
authors.lastname: Witherspoon
authors.forename: P
authors.initials: P
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Kennedy
authors.forename: J J
authors.initials: JJ
authors.lastname: Mond
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology; D003911:Dextrans / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006241:Haptens / Q000008:administration & dosage; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology; D011506:Proteins / Q000008:administration & dosage* / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D003911:Dextrans; D006241:Haptens; C071284:Pfs25 protein, Plasmodium falciparum; D011506:Proteins; D015800:Protozoan Proteins