Enhancement of immune responses using a self-assembled lentinan nano-adjuvant

Adjuvants are critical for enhancing vaccine efficacy, however, conventional adjuvants often suffer from poor biocompatibility and limited immune activation profiles. Herein, we developed a nanoadjuvant by modifying a lentinan (LNT) backbone with polyethyleneimine (PEI) to generate a cationic LNT-PEI vector, which was then used to load SOCS1 siRNA, forming LNT-PEI/siRNA nanocomplexes. In vitro experiments demonstrated that LNT-PEI/siRNA effectively silenced Socs1 gene expression, significantly upregulated the expression of CD80 and CD86, and promoted the secretion of TNF-α and IL-6. Furthermore, a vaccine was formulated by self-assembling the LNT-PEI/siRNA nanoadjuvant with the model antigen ovalbumin (OVA) to evaluate its in vivo immunostimulatory capacity. Biodistribution studies revealed that the vaccine formulation effectively targeted and accumulated in lymph nodes while reducing non-specific hepatic retention. Immunological evaluation showed that incorporation of LNT-PEI/siRNA markedly increased the proportions of CD11b⁺F4/80⁺ macrophages and CD11c⁺ dendritic cells, as well as CD3⁺CD8a⁺ T cells in the spleen. It also upregulated costimulatory molecule expression and elevated serum levels of TNF-α, IL-6, and IFN-γ. In summary, the LNT-PEI/siRNA nanoadjuvant developed in this study successfully enhances immune responses, providing both a theoretical foundation and experimental basis for the development of next-generation vaccine adjuvants.