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 antigens inducing both MHC class I and class II restricted immune responses. Protective immunity has been evoked against a variety of infectious agents. The saponin adjuvant Quil A, which was originally used to form iscoms, is composed of a mixture of structurally similar triterpenoids from Quillaja saponaria Molina having different biological activities. A purified, toxic Quillaja triterpenoid fraction with strong adjuvant activity, designated QH-B, was used to study whether modification of the carbohydrate moiety with sodium periodate would alter the toxicity without 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 periodate 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 and 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 doses tested. However, the use of modified QH-B as described in the present study for iscom-matrix formation resulted in "saponin-lipid complexes" which, to a various degree or totally, deviated from the characteristic iscom morphology.
Rönnberg
B
B
Department of Iscom Technology, National Veterinary Institute, Uppsala, Sweden.
Fekadu
M
M
Behboudi
S
S
Kenne
L
L
Morein
B
B
D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D015941:Complement Hemolytic Activity Assay; D005260:Female; D016882:ISCOMs / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010504:Periodic Acid / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012503:Saponins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D002241:Carbohydrates; D016882:ISCOMs; D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; D010504:Periodic Acid; D002784:Cholesterol; C009288:metaperiodate