Polyethyleneimine-modified Laminarin nanoparticles as a novel vaccine adjuvant for ovalbumin to enhance the immune responses

Functional modification of drugs can significantly improve their efficacy and safety, thus enabling targeted therapy. Functional modifications based on polysaccharides can alter their molecular structure, and effectively enhance their functional properties and biological activities. Herein, we designed and synthesized cationic Laminarin (CLam) modified with polyethyleneimine (PEI) and explored its application as a vaccine adjuvant. The PEI modification resulted in a positively charged surface of CLam, which was mixed with model antigen (Ovalbumin, OVA) to form CLam/OVA nanoparticles with an optimal particle size of about 380.07 nm, a uniform distribution of the particle size and a stable system. In vitro experiments showed that the positive charge on the surface of CLam/OVA enabled it to be effectively internalized by bone marrow dendritic cells (BMDCs), promoted cell maturation, lysosomal escape, and the efficiency of antigen cross-presentation. Mechanically, CLam/ OVA induces BMDC function via toll-like receptors, cytokine receptors, and chemokine-mediated signaling pathways. CLam/OVA induced stronger humoral and cellular immunity compared to the aluminum adjuvant. CLam/OVA induces higher levels of OVA-specific antibodies, generates cytotoxic T lymphocyte immune responses, and stimulates IFN-gamma secretion. Overall, this study demonstrates that functionalization is critical for the rational design of polysaccharides to boost antigen-specific immune responses for more effective and long-lasting vaccination.