Polygonatum sibiricum Polysaccharide and αGalCer Synergistically Act as Dual Adjuvants to Enhance Humoral and Cellular Immune Responses

Adjuvants are indispensable for subunit vaccines. However, the development of safe and effective adjuvants remains a major challenge. Polysaccharides derived from traditional Chinese medicine (TCM) have recently emerged as promising sources of novel vaccine adjuvants. In this study, we investigated the adjuvant activity of Polygonatum sibiricum polysaccharide (PSP) in combination with the glycolipid α-galactosylceramide (αGalCer or αGC). In vitro, PSP significantly promoted the activation of RAW264.7 and DC2.4 cells. In vivo, the PSP/αGC dual adjuvant group elicited markedly stronger cytokine production and a more robust humoral immune response compared with the single adjuvant groups. Moreover, it induced a strong cellular immune response with a balanced Th1/Th2 response and enhanced memory T-cell responses. The dual-adjuvant system also demonstrated a good biocompatibility and safety in mice. To our knowledge, this is the first report of a dual-adjuvant system combining a plant-derived polysaccharide with an iNKT cell agonist, highlighting PSP/αGC as a promising platform for next-generation vaccine design.