Yu You-Bo, Liu Ying, Liang Hangeri, Dong Xianxin, Yang Xiao-Yan, Li Sha, Guo Zhong
Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai, Guangdong, China.
Zhuhai Key Laboratory of Basic and Applied Research in Chinese Medicine, College of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, China.
Microbiol Spectr. 2023 Mar 28;11(2):e0432822. doi: 10.1128/spectrum.04328-22.
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 and . 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. 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 and . The findings will help in prevention of dental caries and provide new insight for the development of anticaries vaccine in the future.
龋齿疫苗已被确定为一种通过接种针对变形链球菌的疫苗来预防龋齿的良好策略，变形链球菌是导致龋齿的主要病原菌。变形链球菌的蛋白抗原c（PAc）已被用作抗龋齿疫苗，但显示出相对较弱的免疫原性，只能引发低水平的免疫反应。在此，我们报告了一种基于沸石咪唑酯骨架-8纳米颗粒（ZIF-8 NP）的佐剂，它具有良好的生物相容性、pH响应性以及对PAc的高负载性能，被用作抗龋齿疫苗。在本研究中，我们制备了ZIF-8@PAc抗龋齿疫苗，并研究了该疫苗诱导的免疫反应和抗龋齿效果。ZIF-8纳米颗粒显著提高了PAc在溶酶体中的内化，以便进一步加工并呈递给T淋巴细胞。此外，皮下注射ZIF-8@PAc的小鼠体内检测到的IgG抗体滴度、细胞因子水平、脾细胞增殖指数以及成熟树突状细胞（DCs）和中枢记忆T细胞的百分比均显著高于单独皮下注射PAc的小鼠。最后，用ZIF-8@PAc对大鼠进行免疫，ZIF-8@PAc引发了强烈的免疫反应，抑制了变形链球菌的定植，并提高了对龋齿的预防效果。基于这些结果，ZIF-8纳米颗粒有望成为抗龋齿疫苗开发的佐剂。变形链球菌是龋齿的主要病原菌，其蛋白抗原c（PAc）已被用作抗龋齿疫苗。然而，PAc的免疫原性相对较弱。为了提高PAc的免疫原性，使用ZIF-8纳米颗粒作为佐剂，并评估了ZIF-8@PAc抗龋齿疫苗引发的免疫反应和保护作用。这些发现将有助于预防龋齿，并为未来抗龋齿疫苗的开发提供新的见解。
