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

Area of Science:

• Vaccinology
• Nanotechnology
• Immunology

Background:

• Conventional vaccine adjuvants face challenges with biocompatibility and limited immune activation.
• Developing novel adjuvants is crucial for improving vaccine efficacy and safety.

Purpose of the Study:

• To develop and evaluate a novel nanoadjuvant based on lentinan (LNT) and polyethyleneimine (PEI) for enhanced vaccine efficacy.
• To investigate the potential of LNT-PEI/siRNA nanocomplexes as a next-generation vaccine adjuvant.

Main Methods:

• Synthesized LNT-PEI/siRNA nanocomplexes by modifying a lentinan backbone with polyethyleneimine and loading SOCS1 siRNA.
• Evaluated *in vitro* gene silencing, immune cell marker expression (CD80, CD86), and cytokine secretion (TNF-α, IL-6).
• Formulated a vaccine with the nanoadjuvant and ovalbumin (OVA) antigen, assessing *in vivo* biodistribution, immune cell populations (macrophages, dendritic cells, T cells), and serum cytokine levels (TNF-α, IL-6, IFN-γ).

Main Results:

• LNT-PEI/siRNA effectively silenced *Socs1* gene expression *in vitro*, upregulating CD80, CD86, TNF-α, and IL-6.
• The nanoadjuvant targeted lymph nodes *in vivo*, reducing hepatic accumulation.
• Incorporation of LNT-PEI/siRNA significantly boosted immune cell populations (macrophages, dendritic cells, CD8+ T cells) and elevated serum cytokine levels (TNF-α, IL-6, IFN-γ).

Conclusions:

• The developed LNT-PEI/siRNA nanoadjuvant demonstrates significant potential for enhancing vaccine-induced immune responses.
• This study provides a strong foundation for the development of advanced vaccine adjuvants with improved biocompatibility and immunogenicity.