An Injectable Chitosan Hydrochloride-Sodium Alginate Hydrogel Adjuvant Capable of Eliciting Potent Humoral and Cellular Immunity

Adjuvants can enhance the immune effects of vaccines. Currently, the most commonly used and validated are aluminum and oil-emulsion adjuvants. However, these adjuvants are not without flaws; for instance, aluminum adjuvants can cause adverse reactions and irritation at the injection site. Consequently, the development of new, safe, and effective adjuvants remains a prominent topic in vaccine research. In this study, we synthesized a composite hydrogel by combining sodium alginate (SA) and the chitosan derivative chitosan hydrochloride (CHCL) to explore the feasibility of this polymer composite hydrogel as a novel immunoadjuvant. Our results indicate that this hydrogel material possesses good biocompatibility and antibacterial properties, is easily injectable, and locally initiates vaccine responses by stimulating the phagocytosis of protein antigens by dendritic cells (DCs). Additionally, they offer sustained exposure to vaccine antigens. After administration, a transient inflammatory niche is created to prolong immune system activation. Importantly, our study demonstrated that the CHCL-SA hydrogel loaded with antigens effectively stimulated the body to produce a humoral immune response and enhance the maturation of the CD8+ T lymphocyte subset. In murine tumor challenge experiments, the CHCL-SA supplemented antigen group significantly inhibited tumor cell growth and improved mouse survival rates. In summary, we developed an injectable CHCL-SA hydrogel adjuvant with great potential for enhancing the efficacy of vaccines.