<i>Polygonatum sibiricum</i> 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 <i>Polygonatum sibiricum</i> polysaccharide (PSP) in combination with the glycolipid α-galactosylceramide (αGalCer or αGC). <i>In vitro</i>, PSP significantly promoted the activation of RAW264.7 and DC2.4 cells. <i>In vivo</i>, 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.