DNA immunization with plasmids expressing hCGbeta-chimeras.
Human chorionic gonadotropin has been used as an anti-fertility vaccine and as a target for cancer immunotherapy. We have explored the use of DNA immunization with the aim of improving the immunogenicity of this hormone. Stimulating the muscle with electric pulses following intramuscular injection of plasmids expressing hCGbeta resulted in higher levels of human chorionic gonadotropin (hCG)-specific antibodies, which could be further enhanced following a protein boost with hCG mixed with adjuvant. DNA vaccines encoding a membrane attached or a secreted form of hCGbeta produced similar-albeit relatively modest-antibody responses. Providing hCGbeta with additional T cell help by vaccinating with a plasmid encoding a hCGbeta-hFc fusion protein did not further increase the antibody levels in the immunized animals. However, immunization of mice with a construct encoding hCGbeta fused to C3d(3) produced significantly lower antibody levels relative to mice immunized with the hCGbeta-alone expression plasmid, even though the hCGbeta-C3d(3) chimera was expected to facilitate cross-linking of the antigen-specific B-cell receptor and CR2 thereby lowering the threshold of activation. Thus the limiting factor determining the antibody levels following hCGbeta immunization, at least for DNA immunization, is related to the amount of protein available rather than the form of protein produced or lack of T cell epitopes.
Terrazzini
Nadia
N
Department of Immunology and Molecular Pathology, University College London, 46 Cleveland Street, London W1T 4JF, UK.
Hannesdóttir
Sólveig
S
Delves
Peter J
PJ
Lund
Torben
T
D000276:Adjuvants, Immunologic; D000818:Animals; D000906:Antibodies / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015933:Complement C3d / Q000235:genetics / Q000276:immunology; D004558:Electric Stimulation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007117:Immunization, Secondary; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010957:Plasmids; D017464:Receptors, Complement 3d / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000906:Antibodies; D018997:Chorionic Gonadotropin, beta Subunit, Human; D018984:Epitopes, T-Lymphocyte; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D017464:Receptors, Complement 3d; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D015933:Complement C3d