Enhancement of antibody responses in DNA vaccination using a vector encoding a universal T-helper cell epitope.
DNA vaccination appears as a very promising approach to raise protective antibodies against a variety of proteins from pathogens or tumor cells, but is often hindered by the low immunogenicity of the genetic vectors used for the immunizations. To enhance the humoral response through improvement of the antigenic presentation of newly synthesized proteins upon vaccination, we engineered a plasmid coding for a low immunogenic protein (an scFv, i.e. the single-chain Fragment variable of a well-characterized antibody) fused to a small-size universal T-helper cell epitope derived from tetanus toxin, whose efficiency in classical protein-based immunization protocols has already been demonstrated. We found that immunization of C57Bl/6 mice using this vector greatly enhanced the production not only of specific antibodies recognizing essentially conformational epitopes on the undenatured scFv protein but also of antibodies against linear epitopes on the denatured protein. Since this T-epitope is known to be accommodated by several haplotypes of H-2 molecules in mice, as well as by various class II MHC molecules in humans, the results reported here allow us to conclude that this method could be of general interest for future applications of genetic immunization, including DNA-based vaccinations in humans.
Tymciu
Sylvie
S
CEA, Service de Pharmacologie et d'Immunologie, DSV/DRM, Bât. 136, CEA/Saclay, 91191 Gif-sur-Yvette Cedex, France.
Durieux-Alexandrenne
Coralie
C
Wijkhuisen
Anne
A
Créminon
Christophe
C
Frobert
Yveline
Y
Grassi
Jacques
J
Couraud
Jean-Yves
JY
Boquet
Didier
D
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D001483:Base Sequence; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D010957:Plasmids / Q000235:genetics* / Q000276:immunology; D013744:Tetanus Toxin / Q000235:genetics; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*
D000906:Antibodies; D018076:DNA, Complementary; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D009841:Oligonucleotides; D010446:Peptide Fragments; D013744:Tetanus Toxin; D019444:Vaccines, DNA