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

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 o...

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Bibliographic Details
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
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Summary: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.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2006.11.059