Plant-Derived Saponin and Polysaccharide Vaccine Adjuvants: Structure–Activity Relationships and Immune-Enhancement Strategies

Plant-derived compounds, particularly saponins and polysaccharides, have attracted interest as vaccine adjuvants because of their diverse immunomodulatory activities. Increasing evidence suggests that the immunological activities of these compounds are closely associated with their structural characteristics, highlighting the importance of understanding how structural features influence their interactions with the immune system. Nevertheless, a systematic understanding of the relationships between structural features and immunological activity remains incomplete, limiting the rational development and optimization of plant-derived adjuvants. In addition, their broader development and translation are constrained by challenges such as poor stability, low bioavailability, insufficient immunostimulatory activity, and limited delivery efficiency. Against this background, this review focuses on the structure–activity relationships of plant-derived saponin and polysaccharide adjuvants, with particular emphasis on how key structural features influence the engagement of pattern recognition receptors (PRRs), antigen uptake and presentation, cytokine production, and subsequent humoral and cellular immune responses. Building on these structure–activity relationships, we further discuss current strategies for improving adjuvant performance, including structural modification and derivatization, delivery-system optimization, and combination strategies. Together, these insights provide a structure–activity framework for the rational design and development of more effective next-generation plant-derived saponin and polysaccharide adjuvants.