Elucidating the Mechanisms of Action of Saponin-Derived Adjuvants

Numerous triterpenoid saponins are adjuvants that modify the activities of T cells and antigen-presenting cells, like dendritic cells (DCs). Saponins can induce either proinflammatory Th1/Th2 or sole anti-inflammatory Th2 immunities. Structure-activity relationships (SARs) have shown that imine-forming carbonyl groups are needed for T cell activation leading to induction of Th1/Th2 immunities. While saponins having different triterpenoid aglycons and oligosaccharide chains can activate DCs to induce Th1/Th2 immunoresponses, fucopyranosyl residues from their oligosaccharides by binding to the DC-SIGN receptor can bias DCs toward a sole Th2 immunity. Here we discuss the mechanisms of action of these saponins in view of new information, which may serve as a basis to design improved adjuvants and related drugs.