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The University of Southampton
Chemistry

Research project: Attard: New Adjuvants For Synthetic Vaccines

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Recent developments in biotechnology have enabled the production of bulk quantities of the proteins and oligopeptides that occur on the surfaces of pathogens.

The use of these synthetic chemical species in vaccines is attractive because they are expected to induce a much better defined immune response than is possible using the current generation of vaccines. However, the problem with these soluble proteins and peptides is that they are only weakly immunogenic. Hence, there is considerable interest in designing drugs (adjuvants) that when administered with synthetic peptides promote a vigorous immune response. Our research in this area has focussed on the strong adjuvant properties exhibited by certain types of naturally-occuring glycoside amphiphiles. Through a collaboration with Dr W.J.W. Morrow of the Department of Immunology at St. Bartholomew's Hospital we have been carrying out a systematic study of the relationship between the chemical structures of glycoside amphiphiles, the types of aggregation structures they form, and their adjuvant potency. Through these studies we found that tomatine (an alkaloid glycoside) when mixed with cholesterol and certain phospholipids aggregates into sheet like solid-state structures with a complex porous morphology. Our experiments have shown that the immunostimulatory effects of tomatine-containing systems are of the same order of magnitude as that of the best experimental adjuvant (complete Freund's adjuvant) but without any inflammatory side-effects. In addition we have found that the use of our adjuvant formulation allows synthetic peptides to access the Class I antigen processing pathway. This property shows the viability of a new generation of vaccines which, in addition to stimulating appropriate antibodies, will stimulate cell-mediated immune respones. Current research is aimed at determining the relative contributions of antigen delivery and membrane mediated biochemical processes to the adjuvant activity of tomatine containing formulations.

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