Polysaccharide-based nanosystems as vaccine adjuvants: A review

Vaccines serve as effective tools for preventing infectious diseases, with adjuvants playing a pivotal role in enhancing immunogenicity, reducing antigen dosage, and minimizing adverse reactions. To mitigate the suboptimal efficacy and safety concerns that constrain current adjuvants, novel formulations exhibiting enhanced safety and potency are required for development. Natural polysaccharides have been employed as vaccine adjuvants. Due to inherent biopharmaceutical limitations-including transient systemic exposure, structural instability, rapid clearance kinetics, and suboptimal bioavailability-their clinical translation as vaccine adjuvants remains constrained, resulting in attenuated immunogenicity. Recent advancements in polysaccharide-based nanosystems have attracted significant attention due to their dual functionality: serving as protective antigen-delivery platforms while concurrently acting as immunostimulants to amplify host immunity. These engineered systems encapsulate polysaccharides and antigens within nanosystems, conferring resistance against enzymatic degradation and enabling sustained release to maintain antigen depot effects. Mechanistically, they enhance vaccine efficacy through multiple pathways: activating antigen-presenting cells (APCs), improving antigen uptake efficiency, achieving targeted delivery, and modulating immune responses, thereby synergistically boosting antigen immunogenicity and overall immune performance. This review examines several promising polysaccharide-based nanosystems adjuvants, outlines their applications in vaccines, and emphasizes their immunomodulatory effects. Furthermore, the potential of polysaccharide-based nanosystems provides valuable theoretical insights for the advancement and application of human vaccine adjuvants.