title: Genetic fusion of three tandem copies of murine C3d sequences to diphtheria toxin fragment B elicits a decreased fragment B-specific antibody response.
abstract: Previous studies have demonstrated that the covalent modification of target protein and polysaccharide antigens with the activated complement product C3d results in dramatically enhanced immunogenicity of the target antigens. In this paper, we describe our attempts to enhance the immunogenicity of the non-toxic B fragment of diphtheria toxin (DT-B) by genetic fusion to polypeptides derived from the C3d coding sequence. Contrary to expectations, we found that the antibody responses elicited by immunizing mice with DT-B genetically linked to three tandem copies of C3d-derived sequences were markedly reduced relative to the antibody responses elicited by immunizing mice with DT-B alone. These results demonstrate levels of complexity in the immunomodulatory effects of the complement system that were not apparent in earlier reports on the adjuvant effects of C3d administered to mice as genetic fusions to target antigens, such as hen egg lysozyme, human immunodeficiency virus (HIV) gp120 or influenza virus hemaglutinnin. The data presented herein suggest that C3d may act as a negative regulator, in some immunological contexts, for antibody production in the mammalian host.
authors.affiliation: Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4943, USA. dgor@bu.edu
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Gor
authors.forename: Xuedong
authors.initials: X
authors.lastname: Ding
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Neil S
authors.initials: NS
authors.lastname: Greenspan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology; D015933:Complement C3d / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D004167:Diphtheria Toxin / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics; D050939:Gene Fusion / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D000941:Antigens; D004167:Diphtheria Toxin; D010446:Peptide Fragments; C039171:diphtheria toxin fragment B; D015933:Complement C3d