A Nanoparticle-Based Anticaries Vaccine Enhances the Persistent Immune Response To Inhibit Streptococcus mutans and Prevent Caries

Abstract

Streptococcus mutans is the main etiologic bacterium of dental caries, whose protein antigen c (PAc) has been administered as an anticaries vaccine. However, the immunogenicity of PAc is relatively weak. Caries vaccines have been identified as a good strategy for the prevention of caries through the mechanism of inoculation against Streptococcus mutans , which is the main etiological bacterium causing caries. Protein antigen c (PAc) of S. mutans has been administered as an anticaries vaccine but shows relatively weak immunogenicity to elicit a low-level immune response. Here, we report a zeolitic imidazolate framework-8 nanoparticle (ZIF-8 NP)-based adjuvant with good biocompatibility, pH responsiveness, and high loading performance for PAc that was used as an anticaries vaccine. In this study, we prepared a ZIF-8@PAc anticaries vaccine and investigated the immune responses and anticaries efficacy induced by this vaccine in vitro and in vivo . ZIF-8 NPs substantially improved the internalization of PAc in lysosomes for further processing and presentation to T lymphocytes. In addition, significantly higher IgG antibody titers, cytokine levels, splenocyte proliferation indices, and percentages of mature dendritic cells (DCs) and central memory T cells were detected in mice subcutaneously immunized with ZIF-8@PAc than in mice subcutaneously immunized with PAc alone. Finally, rats were immunized with ZIF-8@PAc, and ZIF-8@PAc elicited a strong immune response to inhibit colonization by S. mutans and improve prophylactic efficacy against caries. Based on the results, ZIF-8 NPs are promising as an adjuvant for anticaries vaccine development. IMPORTANCE Streptococcus mutans is the main etiologic bacterium of dental caries, whose protein antigen c (PAc) has been administered as an anticaries vaccine. However, the immunogenicity of PAc is relatively weak. To improve the immunogenicity of PAc, ZIF-8 NP was used as an adjuvant, and the immune responses and protective effect elicited by ZIF-8@PAc anticaries vaccine were evaluated in vitro and in vivo . The findings will help in prevention of dental caries and provide new insight for the development of anticaries vaccine in the future.