QS-21 structure/function studies: effect of acylation on adjuvant activity.
QS-21 is a natural saponin adjuvant derived from the tree Quillaja saponaria Molina. Previous studies over a limited dose range suggested the acylation is critical to adjuvant activity. In this study, we prepared DS-1 (deacylated QS-21) and RDS-1 (reacylated DS-1 with dodecylamine at a different site than QS-21) to determine the effect on a dose-response curve over a wider range in mice. DS-1 and RDS-1 induced IgG1 responses at higher doses compared to that induced by QS-21. DS-1 was inactive for inducing IgG2a or CTL responses at any doses. RDS-1 showed moderate IgG2a response at 240 microg, but did not show CTL response at any dose evaluated.
Liu
Gui
G
Antigenics Inc., 175 Crossing Boulevard, Framingham, MA 01702-4473, USA. gliu@antigenics.com
Anderson
Christine
C
Scaltreto
Heidi
H
Barbon
Jeffrey
J
Kensil
Charlotte R
CR
D000215:Acylation; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D000276:Adjuvants, Immunologic; D012503:Saponins; C078785:saponin QA-21V1; D010047:Ovalbumin