QS-21 (Quillaja saponaria saponin fraction 21) (QS-21)

QS-21 is a highly purified saponin fraction derived from the bark of the Quillaja saponaria Molina tree, widely recognized as a potent vaccine adjuvant (Lacaille-Dubois, 2019). It does not target a single protein receptor but instead engages the plasma membranes of innate immune cells, such as dendritic cells and macrophages, by interacting with cholesterol (Welsby et al., 2016). This interaction facilitates the internalization of QS-21, leading to lysosomal destabilization and the release of lysosomal enzymes like cathepsin B into the cytosol (Welsby et al., 2016). This process triggers the activation of the NLRP3 inflammasome, resulting in the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18, which are essential for the induction of robust Th1-type cellular and humoral immune responses (Marty et al., 2023). QS-21 is a critical component of the AS01 adjuvant system used in high-efficacy vaccines like Shingrix (herpes zoster) and Mosquirix (malaria) (GSK, 2023). Despite its efficacy, its use is limited by its inherent hemolytic activity and the complexity of its chemical structure, which necessitates careful formulation in liposomes to ensure safety (Wang, 2021).

Other names

Quillaja saponaria Molina fraction 21QS21Quillaja saponin 21StimulonInnate immune cells and membranes engaged by Quillaja saponaria Molina fraction 21

QS-21 interacts with membrane cholesterol to induce endocytosis and lysosomal destabilization, leading to the release of cathepsin B and subsequent activation of the NLRP3 inflammasome (Welsby et al., 2016).