EFFECTS OF CARBOHYDRATE MODIFICATION OF QUILLAJA-SAPONARIA MOLINA QH-B FRACTION ON ADJUVANT ACTIVITY, CHOLESTEROL-BINDING CAPACITY AND TOXICITY

The iscom is an efficient antigen-presenting system for various antige ns inducing both MHC class I and class II restricted immune responses. Protective immunity has evoked against a variety of infectious agents . The saponin adjuvant Quil A, which was originally used to form iscom s, is composed of a mixture of structurally similar triterpenoids from Quillaja saponaria Molina having different biological activities. A p urified, toxic Quillaja triterpenoid fraction with strong adjuvant act ivity, designated QH-B, was used to study whether modification of the carbohydrate moiety with sodium periodate would alter the toxicity wit hout harming adjuvant activity and cholesterol-binding capacity. Most sugars, and in particular Api, Gal and Xyl, were modified by periodate treatment with only minor changes of the molecular weights indicating no loss of sugar residues. The adjuvant activity of QH-B was reduced in a dose-related manner, and at a concentration of 25 mM sodium perio date a significant reduction in toxicity was observed. The differences in both toxicity and adjuvant activity of the periodate-treated QH-B could be derived from alterations in the structure of the sugars Gal a nd Xyl, while modification of Api may influence adjuvant activity but not toxicity in vivo. The cholesterol-binding capacity, a prerequisite for iscom formation, was not affected by periodate oxidation at the d oses tested. However, the use of modified QH-B as described in the pre sent study for iscom-matrix formation resulted in ''saponin-lipid comp lexes'' which, to a various degree or totally, deviated from the chara cteristic iscom morphology. (C) 1997 Elsevier Science Ltd.