Gürsel, Mayda; (1995) Use of liposomes and cytokines as immunological adjuvants in vaccines. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The potential of liposomes and some of the cytokines as immunological adjuvants was investigated throughout this thesis. Preliminary experiments involved dose response studies with free or liposomally associated tetanus toxoid. Two methods of antigen association with liposomes were used: encapsulation or covalent coupling to the surface of the vesicles. The toxoid was also mannosylated in order to augment targeting of the antigen to macrophages. A low mannose:protein containing product and another one with higher mannose content were used in immunization studies in free, entrapped or surface-linked forms. Next, the potential of giant vesicles as multiple vaccine carriers for particulate and/or soluble antigens was analyzed and compared to results obtained with dehydration-rehydration vesicles. The ability of both carriers to protect their contents from binding of antibodies was also assessed in experiments where the liposomes as such or after treatment with Triton X-100 were incubated with FITC-labelled anti-spore IgG that was raised in rabbit, washed and observed under fluorescence microscope for the presence of antigen-antibody interaction. In the other half of the thesis, the ability of four different cytokines in various liposomal formulations to potentiate the immune responses to the model antigen tetanus toxoid was assessed. IL-1β (163-171) peptide was entrapped or covalently coupled to liposomes. IL-2, IL-12 and IL-15 were also used in various liposomal preparations at different dosages. IL-2 was also used as a co-adjuvant with a synthetic lipidic peptide carrier systen derived from the variable outer membrane protein region of Chlamydia trachomatis as a different antigen.

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