Structure/function studies of QS-21 adjuvant: assessment of triterpene aldehyde and glucuronic acid roles in adjuvant function.
QS-21, a purified Quillaja saponaria saponin immunologic adjuvant, contains two functional groups that we hypothesized to be involved in the adjuvant mechanism of action through charge or Schiff base interaction with a cellular target. Derivatives, prepared by modification of these sites, were prepared and tested for their ability to augment the immunogenicity of the antigen ovalbumin (OVA) in C57BL/6 mice. QS-21 derivatives that were modified at the carboxyl group on an anionic sugar, glucuronic acid, retained adjuvant activity for antibody stimulation, inducing relative increases in antibody titers similar to those induced by QS-21, although the minimum adjuvant dose required for this stimulation was increased several fold relative to the dose of unmodified QS-21. One of these derivatives also retained significant activity for induction of OVA-specific cytotoxic T-lymphocytes. In contrast, QS-21 derivatives modified at an aldehyde on the triterpene did not show adjuvant activity for antibody stimulation or for induction of cytotoxic T-lymphocytes, suggesting that this functional group may be involved in the adjuvant mechanism.
Soltysik
S
S
Cambridge Biotech Corporation, Worcester, MA 01605, USA.
Wu
J Y
JY
Recchia
J
J
Wheeler
D A
DA
Newman
M J
MJ
Coughlin
R T
RT
Kensil
C R
CR
D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D000447:Aldehydes / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D005260:Female; D005965:Glucuronates / Q000737:chemistry / Q000276:immunology*; D020723:Glucuronic Acid; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012503:Saponins / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014315:Triterpenes / Q000737:chemistry / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000447:Aldehydes; D005965:Glucuronates; D015395:Histocompatibility Antigens Class I; D012503:Saponins; D014315:Triterpenes; C078785:saponin QA-21V1; D020723:Glucuronic Acid; D010047:Ovalbumin