A Paris polysaccharide adjuvant enhances vaccine immunogenicity via activating antigen-presenting cells in peripheral tissue and lymph nodes.

The limited availability of safe and effective vaccine adjuvants remains a major bottleneck in modern vaccinology, particularly for inducing balanced and robust cellular and humoral immune responses. This study investigated the adjuvant potential of polysaccharides isolated from Paris mairei (PMM, 740 kDa) and Paris yunnanensis (PPM, 92 kDa). Structural analysis confirmed that both polysaccharides are primarily composed of a (1 → 4)-linked β-D-Man backbone with mannose residues partially acetylated at the O-2 or O-3 positions. However, only PMM effectively activated antigen-presenting cells (APCs). In combination with aluminum hydroxide (AH), PMM enhanced both IgG1 and IgG2a humoral responses and promoted Th1-associated cellular immune responses in Varicella-zoster virus glycoprotein E (VZV gE) models. Mechanistic studies revealed that AH functions as a local antigen depot, while soluble PMM accumulates in draining lymph nodes to activate APCs. PMM-induced macrophage activation involves TLR4 signaling, accompanied by NF-κB/MAPK activation and M1 polarization. This study identifies Paris-derived polysaccharides as promising innate immune modulators and provides a feasible polysaccharide-AH combination strategy for improving vaccine adjuvant design.