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

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.

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 responses 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 antibodies, a higher splenocyte proliferation index, higher levels of the cytokines IL-4, IL-6, IL-10, IL-17A and IFN-γ, 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.

Immunization with the lipoprotein FtsB stimulates protective immunity against Streptococcus pyogenes infection in mice.

Streptococcus pyogenes is one of the main pathogenic bacteria that causes disease in humans. It is reported that over 18 million cases of S. pyogenes disease occurred in the world, and more than 500,000 deaths occur annually worldwide. An effective vaccine is widely regarded as the most reliable way to control and prevent streptococcal infections. However, there is currently no approved vaccine for S. pyogenes. In this study, we evaluated the potential of lipoprotein FtsB as a new vaccine candidate to prevent S. pyogenes infection. Mice vaccinated with purified FtsB protein elicited high titers of IgG, IgG1 and IgG2a antibodies in mouse serum. Vaccinated with FtsB can reduce bacterial systemic dissemination in the blood, heart, and spleen and reduce organ damage in the mouse bacteremia model. In addition, active immunization with FtsB protected against streptococcal abscess formation. Furthermore, immunization with FtsB was efficient in inducing a mixed cellular immune response and promoting the maturation of dendritic cells in mice. The lipoprotein HtsA was served as a positive control because it has been reported to protect mice from S. pyogenes infection in both active and passive immunization. These findings demonstrated that lipoprotein FtsB may serve as a candidate vaccine for the prevention of S. pyogenes infection.