Hu, Y., et al. QS-21: Structural insights, immunological mechanisms, and prospects for rational design of safer vaccine adjuvants. Eur J Med Chem, 2025 Oct 2, 301:118223.

Hu, Y., et al. QS-21: Structural insights, immunological mechanisms, and prospects for rational design of safer vaccine adjuvants. Eur J Med Chem, 2025 Oct 2, 301:118223. PMID: 41046625

• This review provides a comprehensive overview of QS-21, a potent saponin adjuvant derived from the bark of Quillaja saponaria, highlighting its significant role in eliciting robust Th1 and Th2 immune responses in vaccine formulations. It discusses the structural features of QS-21, including key functional domains critical for its immunostimulatory activity, and explores current understandings of its mechanisms of action, such as activation of dendritic cells and induction of inflammasome pathways. The review addresses major challenges hindering its widespread application, including limited natural availability, chemical instability, dose-limiting toxicity, and complex purification processes. To overcome these hurdles, recent advances in chemical synthesis, semi-synthetic derivatives, and biosynthetic methods using engineered yeast strains are examined. Furthermore, the paper emphasizes ongoing efforts to optimize QS-21 analogs for improved safety, stability, and efficacy, as well as strategies for rational design.
  
• Future research should focus on elucidating its molecular mechanisms of action, optimizing structural modifications, and designing safer, more stable analogs. These efforts aim to facilitate the rational development of next-generation adjuvants that are safer, more effective, and accessible for global vaccination programs.

Click here to access the full scientific paper.