Fusion of antigen to Fas-ligand in a DNA vaccine enhances immunogenicity.
DNA vaccines have considerable potential for the prophylaxis and therapy of a range of diseases, but their potential has not been realised largely due to poor immunogenicity. Fas ligand is a pro-apoptotic molecule, able to induce death of Fas expressing cells. We describe the construction of a DNA vaccine encoding a chimeric fusion between Fas ligand and a truncated version of HIV gp120 as a model antigen. The fusion DNA was used as a priming vaccine, along with boosting with recombinant gp120 protein. Priming with fusion protein DNA resulted in a powerful enhancement of immune responses to the protein boost, and, in the presence of aluminum phosphate, to a strong enhancement in T helper 2 type responses. Fas ligand delivered in a separate plasmid also had an adjuvant effect, although it was weaker than that delivered by the fusion protein.
Nimal
Sonali
S
Unit of Infection and Immunity, University of Sheffield Medical School, Sheffield S10 2RX, UK.
Thomas
Mark S
MS
Heath
Andrew W
AW
D017607:Aluminum Compounds / Q000276:immunology; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology*; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D010710:Phosphates / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*
D017607:Aluminum Compounds; D016207:Cytokines; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D010710:Phosphates; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C012714:aluminum phosphate