Immunological properties of Quillaja saponins

Quillaja saponin has for a long time been used as adjuvant in animal vaccines and is now a candidate for use in human vaccines. Quillaja saponin is extracted from the bark of the tree Quillaja saponaria Molina and consists of a glycosylated quillaic acid. Quillaja saponin is the unique component of the immunostimulating complex (iscom). Iscom is composed of Quillaja saponin, cholesterol, phosphatidylcholine and antigens. In general, Quillaja formulations, i.e. free Quillaja saponin, iscom and iscom-matrix (antigen-free iscom) enhance both antibody and cell mediated responses but their capacities to enhance these responses differ. Iscom is the most potenet of the Quillaja saponin formulations. The proportion of the various Quillaja saponins in iscom-matrix or iscom has a profound effect on the immunoenhancing capacity of Quillaja saponin formulations. Therefore, it was crucial to design and employ methods to efficiently isolate and accurately quantify Quillaja saponin and lipids in iscom-matrix and iscoms. A periodate oxidation procedure was employed to modify the monosaccharides of the carbohydrates of Quillaja saponin in a step wise manner. The modification resulted in decrease of adjuvant activity and toxic effects in a step wise, while cholesterol binding capacity remained unchanged. Proinflammatory cytokinins such as IL-1, IL-6 and IL-12 play important roles in the stimulatin of B cell and T cell responses. These cytokines are produced by antigen presenting cells (APCs) upon stimulation with antigens and/or adjuvants. Comparative studies showed that iscoms were more efficient than other Quillaja saponin formulations in the induction of IL-1, IL-6 and IL-12 production. This result indicates that immunoenhancing capacity is greater when antigen and adjuvant are presented in the same particle. The capacity of iscom to stimulate IL-12 production is an important feature of its immunomodulatory activity. QH-A was more efficient than QH-C in the induction of IL-1 and IL-6. This difference may explain the magnitudes of and/or the types of immune responses induced by these defined Quillaja saponins. Interestingly, the QH 7.0.3 formulation, when incorporated into iscom-matrix resulted in the most potent iscom-matrix formulation with respect to induction of APC to produce cytokines.