Fusion of antigen to Fas-ligand in a DNA vaccine enhances immunogenicity

• Published in: Vaccine 2007-03, Vol.25 (12), p.2306-2315
• Main Authors: Nimal, Sonali, Thomas, Mark S, Heath, Andrew W
• Format: Article
• Language: English
• Subjects: Adjuvant; Allergy and Immunology; Aluminum; Aluminum Compounds - immunology; Animals; Antigen presentation; Apoptosis; Applied microbiology; Biological and medical sciences; Cell Line; Cercopithecus aethiops; COS Cells; Cytokines - metabolism; Deoxyribonucleic acid; DNA; Enzyme-Linked Immunosorbent Assay; Fas Ligand Protein - genetics; Fas Ligand Protein - immunology; FasL; Female; Fundamental and applied biological sciences. Psychology; Genes; gp120; HIV; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - immunology; Human immunodeficiency virus; Immunogenicity; Immunoglobulin G - immunology; Interferon; Ligands; Male; Mice; Microbiology; Miscellaneous; Phosphates - immunology; Plasmids; Prophylaxis; Proteins; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Th2 Cells - immunology; Th2 Cells - metabolism; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - adverse effects; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2006.11.059

Abstract 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.