Engineering vaccines with heterologous B and T cell epitopes using immunoglobulin genes.
Antibodies engineered in their variable domain to express epitopes of heterologous antigens-antigenized antibodies-function as immunogens. Only the third complementarity-determining region (CDR3) of the H chain has been used as the site of epitope expression, as this loop has the highest natural variability in length and amino acid composition. We demonstrate that the CDR2 can be engineered to express a 12-amino acid peptide, which is a T-cell determinant that enhances the response to a B-cell epitope peptide of Plasmodium falciparum expressed in the CDR3 of the same variable domain. Mice with this gene inoculated into the spleen mounted an antibody response against the B-cell epitope higher than mice receiving the gene coding for the B-cell epitope only. In vitro studies established that the two epitopes were independently immunogenic in vivo.
Xiong
S
S
Department of Medicine and Cancer Center, University of California, San Diego, La Jolla 92093-0063, USA.
Gerloni
M
M
Zanetti
M
M
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D005803:Genes, Immunoglobulin / Q000235:genetics*; D005818:Genetic Engineering; D007376:Interleukin-2 / Q000032:analysis; D051379:Mice; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology; D010957:Plasmids; D010963:Plasmodium falciparum / Q000235:genetics*; D016052:Protozoan Vaccines / Q000235:genetics*; D013154:Spleen / Q000276:immunology; D014162:Transfection; D019076:Transgenes / Q000235:genetics / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D009842:Oligopeptides; D016052:Protozoan Vaccines; C052953:(asparaginyl-alanyl-asparaginyl-proline)3