The Ph-Responsive Zeolitic Imidazolate Framework Nanoparticle As a Promising Immune-Enhancing Adjuvant for Anti-Caries Vaccine

Objectives: Streptococcus mutans (S. mutans) is the main aetiologic bacterium of dental caries, whose protein antigen (PAc) has been administered as an anti-caries vaccine. In addition, several fusion proteins or PAc combined with adjuvants were used as anti-caries vaccines to improve the relatively weak immunogenicity of PAc. However, there are no nanoparticle-based adjuvants with good biocompatibility, excellent biodegradability, or the high loading performance of antigens used for anti-caries vaccines. This study aimed to prepare an innovative nanoparticle-based anti-caries vaccine and evaluate immune responses elicited by this vaccine in vitro and in vivo.Methods: In this study, an anti-caries vaccine was prepared by an antigen of recombinant protein PAc from S. mutans and an adjuvant of zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) synthesized using a hydrothermal method. Then, mice were administrated intranasally by ZIF-8@PAc vaccine, and immune re-sponses were evaluated.Results: ZIF-8 NPs not only greatly improved the internalization of the antigen but also released the PAc protein after degradation of ZIF-8 NPs in lysosomes for the further processing and presentation of antigen-presenting cells. In addition, ZIF-8@PAc induced significantly more potent PAc-specific serum IgG and saliva IgA anti-bodies, a higher splenocyte proliferation index, higher levels of the cytokines IL-4, IL-6, IL-10, IL-17A and IFN-gamma, and a higher percentage of mature DCs and CD4+ memory T cells in vivo.Conclusions: The ZIF-8 NPs, as an anti-caries vaccine adjuvant-assisted antigen PAc, elicit significantly potent immune responses, aiding in the further prevention of dental caries.Clinical significance: Vaccine immunotherapy is an attractive strategy for prevention and treatment of dental caries. The ZIF-8@PAc vaccine can induce significantly high level of immune responses in this study, which indicates great potential for prevention and treatment of caries.