Amplification of immune responses against a DNA-delivered idiotypic lymphoma antigen by fusion to the B subunit of E. coli heat labile toxin.
The pentameric B-subunit of Escherichia coli heat-labile enterotoxin (EtxB) is not only highly immunogenic itself, but can also act as a potent adjuvant or carrier to increase immune responses to other antigens. In this study, we investigated the ability of EtxB to promote anti-tumor immune responses using a fusion DNA vaccine design. EtxB was genetically linked to a single chain Fv sequence derived from the idiotypic immunoglobulin antigen (Id) of the mouse BCL1 B-cell lymphoma. We found that the EtxB-BCL1scFv fusion protein with a specifically selected linker retained the ability to pentamerize and to bind the GM1 ganglioside. Immunization of mice with the pEtxB-BCL1scFv DNA construct generated high levels of Id-specific antibody and protected against lethal tumor challenge. The immuno-enhancing activities of EtxB were highly dependent on GM1 binding, since fusion constructs unable to pentamerize or to bind to GM1 were less effective. Thus, the EtxB fusion vaccine approach may be an attractive strategy to increase the potency of tumor vaccines.
Chen
Caleb G
CG
Department of Hematology-Oncology, Mackay Memorial Hospital, Taipei 10449, Taiwan.
Lu
Yen-Ta
YT
Lin
Marie
M
Savelyeva
Natalia
N
Stevenson
Freda K
FK
Zhu
Delin
D
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D004768:Enterotoxins / Q000235:genetics / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D005677:G(M1) Ganglioside / Q000378:metabolism; D008223:Lymphoma / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D001427:Bacterial Toxins; D019496:Cancer Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D005677:G(M1) Ganglioside; C027538:heat-labile enterotoxin, E coli