title: Differential effects of C3d on the immunogenicity of gene gun vaccines encoding Plasmodium falciparum and Plasmodium berghei MSP1(42).
abstract: The complement fragment C3d mediates B-cell activation via simultaneous engagement of the B-cell receptor and CD21 by antigen/C3d conjugates. Several studies demonstrated the potential of C3d as a molecular adjuvant for vaccination. In this work, C3d exerted differential effects on humoral immune responses after gene gun immunization of mice with plasmids encoding the malaria blood stage antigen MSP1(42) depending on the nature of the protein (Plasmodium falciparum vs. Plasmodium berghei MSP), the localization of the C3d moiety (C-terminal vs. N-terminal), and the presence of putative N-glycosylation sites. No improvement of protective efficacy by C3d attachment or mutation of glycosylation sites could be demonstrated by in vitro parasite growth inhibition assays or in vivo blood stage parasite challenges. Our data underscore the controversial role of C3d as molecular adjuvant.
authors.affiliation: Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Weiss
authors.forename: Maximilian
authors.initials: M
authors.lastname: Gabler
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacobs
authors.forename: Tim-Wolf
authors.initials: TW
authors.lastname: Gilberger
authors.forename: Josef
authors.initials: J
authors.lastname: Thalhamer
authors.forename: Sandra
authors.initials: S
authors.lastname: Scheiblhofer
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000917:Antibody Formation; D015933:Complement C3d / Q000276:immunology*; D005260:Female; D006031:Glycosylation; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010962:Plasmodium berghei / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D015847:Interleukin-4; D015933:Complement C3d; D007371:Interferon-gamma