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.
We have designed and synthesized two analogs (5 and 6) of QS-7, a natural saponin compound isolated from Quillaja saponaria (QS) Molina tree bark. The only structural difference between compound 5 and 6 is that 5 is acetylated at the 3-and 4-O positions of the quillaic acid C28 fucosyl unit while 6 is not. However, the two analogs show significantly different immunostimulant profiles. Compound 5 may potentiate a mixed Th1/Th2 (Th, T helper cells) immune response against the specific antigens while compound 6 may only induce a Th2-biased immunity. These results suggest that the 3-and/or 4-O acetyl groups of the fucosyl unit may play an important role in tuning the adjuvanticity of the QS-7 analogs, and compound 5 can serve as a structurally defined synthetic adjuvant when a mixed Th1/Th2 immune responses is desired.
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