Advancements in saponin-based vaccine adjuvants

Saponin-based adjuvants have emerged as promising candidates for enhancing vaccine efficacy by modulating immune responses. Derived primarily from plant and marine sources, saponins possess unique amphiphilic structures that contribute to their potent immunostimulatory properties. This review explores the advancements in saponin-based vaccine adjuvants, focusing on their immunomodulatory mechanisms, structural diversity, and applications. QS-21, a triterpenoid saponin from Quillaja saponaria, is the most extensively studied and has been incorporated into licensed vaccines such as Shingrix, Mosquirix, and Arexvy. However, the limitations of natural saponin-derived adjuvants, including hemolytic toxicity, hydrolytic instability, and low yield, have driven research toward semi-synthetic and synthetic analogs. Advances in synthetic biology and biosynthetic pathway elucidation have enabled the development of next-generation saponin-based adjuvants with enhanced potency and reduced toxicity. This review provides a comprehensive overview of the current state of saponin-based adjuvant research, highlighting their potential to revolutionize vaccine formulations and contribute to global public health initiatives.