Synthesis and Evaluation of a QS-17/18-Based Vaccine Adjuvant

We
have synthesized a QS-17/18 analogue (7) and evaluated
its adjuvant activity in the formulation with rHagB antigen. Compound 7 and QS-21 analogues 5 and 6 are
presumably the major components of GPI-0100, a widely used complex
mixture of semisynthetic derivatives of Quillaja saponaria (QS) Molina saponins. The QS-17/18 analogue 7 shows
an adjuvant activity profile similar to that of GPI-0100, potentiating
mixed Th-1/Th-2 immune responses, which is different from those of
QS-21 analogues 5 and 6 that probably only
induce a Th2-like immunity. The combination of QS-17/18 and QS-21
analogues does not show a synergistic effect. These results suggest
that QS-17/18 analogue 7 might be the active component
of GPI-0100 responsible for its immunostimulant property. Therefore,
compound 7 can not only be a structurally defined alternative
to GPI-0100 but also provide a valuable clue for rational design of
new QS-based vaccine adjuvants with better adjuvant properties.