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Doctoral thesis, 1997

Immunological properties of Quillaja saponins

Behboudi, Shahriar

Abstract

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 die bark of the tree Quillaja saponaria Molina and consists of a glycosylated qirillaic add. 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 Le. 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 potent 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 maimer, while cholesterol binding capacity remained unchanged.

Proinflammatory cytokines such as IL-1, IL-6 and IL-12 play important roles in the stimulation 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 waemore efficientthan 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 ofits 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 ofAPC to produce cytokines.

Keywords

APC; IL-1; IL-6; IL-12; iscom; iscom-matrix; periodate oxidation; Quillaja saprmin

Published in

Acta Universitatis Agriculturae Sueciae. Veterinaria
1997, number: 12
ISBN: 91-576-5245-7
Publisher: Swedish University of Agricultural Sciences

Authors' information

Behboudi, Shahriar
Swedish University of Agricultural Sciences, Department of Veterinary Microbiology

UKÄ Subject classification

Pathobiology

URI (permanent link to this page)

https://res.slu.se/id/publ/117377