Differential effects of C3d on the immunogenicity of gene gun vaccines encoding Plasmodium falciparum and Plasmodium berghei MSP1(42).
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.
Weiss
Richard
R
Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
Gabler
Maximilian
M
Jacobs
Thomas
T
Gilberger
Tim-Wolf
TW
Thalhamer
Josef
J
Scheiblhofer
Sandra
S
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
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