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 ... -  《-》

Hydroxypropyltrimethyl ammonium chloride chitosan-based hydrogel as the split H5N1 mucosal adjuvant: Structure-activity relationship.

In this study, 2-hydroxypropyltrimethyl ammonium chloride chitosan (HTCC)-based hydrogel was devised as a mucosal adjuvant for H5N1 vaccine. Aimed to investigate the structure activity relationship between HTCC hydrogel and immune response, we prepared a series of HTCC hydrogel with defined quaternization degrees (DQs, 0%, 21%, 41%, 60%, 80%). Results suggested that with DQ increasing, the positive charge and gelation time of HTCC hydrogel increased but the viscosity decreased. We applied in vivo imaging system and found that the moderate DQ 41% prolonged antigen residence time in nasal cavity, resulting in the most potent systemic responses (IgG, IgG1, IgG2a, HI). While, the lowest DQ 0% produced the best mucosal IgA antibody responses, most likely due to the closer contact with mucosa. Furthermore, the influence of animal gender was also discussed. These data add to the growing understanding of the relationship between physicochemical features of chitosan-based hydrogel and how they influence the immune responses.

Fan Q ，Miao C ，Huang Y ，Yue H ，Wu A ，Wu J ，Wu J ，Ma G ... -  《-》

Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery.

Sayin B ，Somavarapu S ，Li XW ，Thanou M ，Sesardic D ，Alpar HO ，Senel S ... -  《INTERNATIONAL JOURNAL OF PHARMACEUTICS》

Preparation and immunological activity evaluation of an intranasal protein subunit vaccine against ancestral and mutant SARS-CoV-2 with curdlan sulfate/O-linked quaternized chitosan nanoparticles as carrier and adjuvant.

Chitosan and its derivatives are ideal nasal vaccine adjuvant to deliver antigens to immune cells. Previously, we successfully used a chitosan derivative, O-(2-Hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (O-HTCC), and a β-glucan derivative, curdlan sulfate (CS), to prepare a nanoparticle adjuvant CS/O-HTCC which could deliver ovalbumin to antigen presenting cells (APCs) through nasal inhalation. In this article, we used SARS-CoV-2 spike receptor binding domain (S-RBD) as the antigen and CS/O-HTCC nanoparticles as the adjuvant to develop a nasal mucosal protein subunit vaccine, CS/S-RBD/O-HTCC. The humoral immunity, cell-mediated immunity and mucosal immunity induced by vaccines were evaluated. The results showed that CS/S-RBD/O-HTCC could induce desirable immunization with single or bivalent antigen through nasal inoculation, giving one booster vaccination with mutated S-RBD (beta) could bring about a broad cross reaction with ancestral and different mutated S-RBD, and vaccination of the BALB/c mice with CS/S-RBD/O-HTCC containing S-RBD mix antigens (ancestral and omicron) could induce the production of binding and neutralizing antibodies against both of the two antigens. Our results indicate that CS/O-HTCC is a promising nasal mucosal adjuvant to prepare protein subunit vaccine for both primary and booster immunization, and the adjuvant is suitable for loading more than one antigen for preparing multivalent vaccines.

Chen Y ，Wang Y ，Li Z ，Jiang H ，Pan W ，Liu M ，Jiang W ，Zhang X ，Wang F ... -  《-》

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 ... -  《-》