Quaternized Chitosan-Coated Nano-MOFs as Antigen Nanocarriers with Enhanced Stability and Immunogenicity.

Abstract

Vaccines are among the greatest achievements of modern medicine, and have saved countless lives. Subunit vaccines are vaccines made from specific parts (subunits) of a pathogen. Compared other types of vaccines, such as inactivated and live-attenuated vaccines, they are generally safer and more suitable for individuals with weakened immune systems. However, their immunogenicity is typically lower, which is why adjuvants are often required to enhance the immune response. Metal-organic frameworks (MOFs), exemplified by zeolitic imidazole framework-90 (ZIF-90), represent an emerging class of porous materials noted for their substantial pore dimensions, freely adjustable particle sizes, excellent chemical stability, biocompatibility, and pH sensitivity of coordination framework dissociation. These features present significant potential for development in the field of vaccine delivery carriers. Chitosan quaternary ammonium salts have good biosafety and can improve immunogenicity. This study successfully encapsulated ovalbumin (OVA) within ZIF-90 using a one-step stirring method to form OVA@ZIF-90 (ZO). Subsequently, the quaternary ammonium salt of chitosan was added to modify ZO through adsorption, resulting in ZIF-90@OVA@HACC (ZOH), which increased the stability and immunogenicity of OVA. Compared with free OVA, ZO and ZOH enhanced the immunogenicity of OVA, promoting the cellular uptake of antigens and escape from lysosomes, activating dendritic cells, stimulating the secretion of cytokines, forming an antigen reservoir to encourage the production of antibodies, and activating CD4⁺ T and CD8⁺ T cells to increase the generation of memory T cells. This study underscores the importance of ZIF-90 and chitosan quaternary ammonium salts in improving the stability and immunogenicity of antigens, which has considerable reference value for the development of subsequent immunizing vaccines.