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, con tains two functional groups that we hypothesized to be involved in the adjuvant mechanism of action through charge or Schiff base interactio n with a cellular target. Derivatives, prepared by modification of the se sites, were prepared and tested for their ability to augment the im munogenicity of the antigen ovalbumin (OVA) in C57BL/6 mice. QS-21 der ivatives 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 induce d by QS-21, although the minimum adjuvant dose required this stimulati on was increased severalfold relative to the dose of unmodified QS-21. One of these derivatives also retained significant activity for induc tion of OVA-specific cytotoxic T-lymphocytes. In contrast, QS-21 deriv atives modified at an aldehyde on the triterpene did not show adjuvant activity for antibody stimulation or for indiction of cytotoxic T-lym phocytes, suggesting that this functional group may be involved in the adjuvant mechanism.