Immunostimulatory effect of chitosan and quaternary chitosan: A review of potential vaccine adjuvants.

Vaccines have always been the most effective preventive treatment. Advancements in the field of vaccine is inseparable from adjuvants. Adjuvants are substances added to vaccines to enhance immunogenicity and induce a stronger immune response. Chitosan fascinated considerable attention as vaccine adjuvant due to its unique physicochemical and biological properties. Many studies have shown that chitosan and its derivatives can effectively activate antigen-presenting cells and induce cytokine stimulation to produce an effective immune response and promote the balance of Th1/Th2 response. Among many derivatives, the quaternized chitosan performs better. This review presents the main factors affecting the adjuvant performance of chitosan and quaternized chitosan firstly. Then, we introduced not only the immune response they may cause, but also their metabolic research in detail. Furthermore, their future prospects are forecasted. Overall, chitosan and quaternized chitosan are both promising adjuvant materials, and quaternized chitosan shows greater potential.

Li X ，Xing R ，Xu C ，Liu S ，Qin Y ，Li K ，Yu H ，Li P ... -  《-》

Chitosan, N,N,N-trimethyl chitosan (TMC) and 2-hydroxypropyltrimethyl ammonium chloride chitosan (HTCC): The potential immune adjuvants and nano carriers.

Vaccine is an important means to prevent diseases, which have attracted the attention of many researchers. However, the immune efficacy of vaccine is limited and requires effective antigen delivery and adjuvant systems to provide appropriate vaccines or immunotherapy antigens for improving the immune efficacy of the mucosal immune system. Recent years, the application of chitosan and its derivatives in immunization have attracted a lot of attention. Many research results proved that chitosan and its derivatives were promising vaccine adjuvants and carriers, which improved immune response for its promising mucoadhesive properties. Among the derivatives, TMC and HTCC are currently the most studied quaternized chitosans. In the first part of our review, we elucidate the preparation methods of chitosan, TMC and HTCC and the factors that may affect their immunity. In the second part, not only we introduce their application as adjuvants and carriers to improve the efficacy of vaccines, but also their application as surface modification materials to improve immune response. All in all, we hold that chitosan, TMC and HTCC are promising biomaterials that can be used to improve immune efficacy, of which TMC may have good development potential.

Zhao J ，Li J ，Jiang Z ，Tong R ，Duan X ，Bai L ，Shi J ... -  《-》

Recent advances on chitosan as an adjuvant for vaccine delivery.

Chitosan (CS) is a natural polymer derived from chitin that has wide applications in drugs, vaccines, and antigen delivery. The distinctive mucoadhesive, biocompatibility, biodegradable, and less toxic properties of chitosan compared to the currently used vaccine adjuvants made it a promising candidate for use as an adjuvant/carrier in vaccine delivery. In addition, chitosan exhibits intrinsic immunomodulating properties making it a suitable adjuvant in preparing vaccines delivery systems. Nanoparticles (NPs) of chitosan and its derivatives loaded with antigen have been shown to induce cellular and humoral responses. Versatility in the physicochemical properties of chitosan can provide an excellent opportunity to engineer antigen-specific adjuvant/delivery systems. This review discusses the recent advances of chitosan and its derivatives as adjuvants in vaccine deliveryand the published literature in the last fifteen years. The impact of physicochemical properties of chitosan on vaccine formulation has been described in detail. Applications of chitosan and its derivatives, their physicochemical properties, and mechanisms in enhancing immune responses have been discussed. Finally, challenges and future aspects of chitosan use has been pointed out.

Dmour I ，Islam N 《-》

Curdlan sulfate-O-linked quaternized chitosan nanoparticles: potential adjuvants to improve the immunogenicity of exogenous antigens via intranasal vaccination.

Zhang S ，Huang S ，Lu L ，Song X ，Li P ，Wang F ... -  《International Journal of Nanomedicine》

Development of a novel adjuvanted nasal vaccine: C48/80 associated with chitosan nanoparticles as a path to enhance mucosal immunity.

In a time in which mucosal vaccines development has been delayed by the lack of safe and effective mucosal adjuvants, the combination of adjuvants has started to be explored as a strategy to obtain potent vaccine formulations. This study describes a novel adjuvant combination as an effective approach for a nasal vaccine - the association of the mast cell activator compound 48/80 with chitosan based nanoparticles. It was hypothesized that mucoadhesive nanoparticles would promote the cellular uptake and prolong the antigen residence time on nasal cavity. Simultaneously, mast cell activation would promote a local microenvironment favorable to the development of an immune response. To test this hypothesis, two different C48/80 loaded nanoparticles (NPs) were prepared: Chitosan-C48/80 NP (Chi-C48/80 NP) and Chitosan/Alginate-C48/80 NP (Chi/Alg-C48/80 NP). The potential as a vaccine adjuvant of the two delivery systems was evaluated and directly compared. Both formulations had a mean size near 500nm and a positive charge; however, Chi-C48/80 NP was a more effective adjuvant delivery system when compared with Chi/Alg-C48/80 NP or C48/80 alone. Chi-C48/80 NP activated mast cells at a greater extent, were better internalized by antigen presenting cells than Chi/Alg-C48/80 NP and successfully enhanced the nasal residence time of a model antigen. Superiority of Chi-C48/80 NP as adjuvant was also observed in vivo. Therefore, nasal immunization of mice with Bacillus anthracis protective antigen (PA) adsorbed on Chi-C48/80 NP elicited high levels of serum anti-PA neutralizing antibodies and a more balanced Th1/Th2 profile than C48/80 in solution or Chi/Alg-C48/80 NP. The incorporation of C48/80 within Chi NP also promoted a mucosal immunity greater than all the other adjuvanted groups tested, showing that the combination of a mast cell activator and chitosan NP could be a promising strategy for nasal immunization.

Bento D ，Staats HF ，Gonçalves T ，Borges O ... -  《-》