Obrenovic, Milka Mia; (2001) Niosomes as a delivery system for DNA vaccines. Doctoral thesis (Ph.D.), University College London.

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Abstract

DNA vaccines have become the spotlight in vaccinology in the past ten years as an alternative to conventional vaccines. In our study we characterized newly formulated non-ionic surfactant vesicles (niosomes) and assessed their potential as a delivery vehicle for DNA vaccines. Plasmid DNA was successfully entrapped into cationic niosomes using the dehydration-rehydration method. The DRV niosomes entrapping or complexing the plasmid DNA were shown to protect the latter from deoxyribonuclease attack as well as damage from probe sonication. Although niosome stability was composition dependent, overall all formulations were more stable in skeletal muscle extract than in plasma at 37°C. Niosomes were shown to offer significant protection to the incorporated plasmid DNA in the presence of plasma and skeletal muscle extract at 37°C. Tissue distribution with 125I-labelled DNA studies indicated that the plasmid DNA is recovered in the injection site as well as the local lymph nodes. Also expression of a plasmid DNA (pEGFP encoding the enhanced green fluorescent protein) after intramuscular injection occurred in the thigh muscle and local lymph nodes to a greater extent compared to the naked DNA. After immunization with cationic DRV niosomes entrapping the plasmid DNA results indicated significantly greater IgG antibody responses against the encoded antigen compared to naked plasmid DNA. The presence of DOPE was shown to be vital for better immune response. Furthermore, production of endogenous IL-4 and IFN-γ cytokines was also detected in the spleen. The cytokine levels were mainly significantly higher in animals injected with niosomal-DNA compared to those injected with naked DNA. It appears that niosome mediated DNA immunization is effective in inducing both humoral and/or cell-mediated immune response and, therefore, niosomes are promising vehicles for the delivery of DNA vaccines.

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