目标:变形链球菌(S.变形)是龋齿的主要病原细菌,其蛋白质抗原(PAc)已作为防龋疫苗施用。此外,将几种融合蛋白或PAc联合佐剂用作防龋疫苗,以改善PAc相对较弱的免疫原性。然而,没有基于纳米颗粒的佐剂具有良好的生物相容性,优异的生物降解性,或用于防龋疫苗的抗原的高负载性能。本研究旨在制备一种创新的基于纳米颗粒的防龋疫苗,并评估该疫苗在体外和体内引起的免疫反应。
方法:在本研究中,通过来自变形链球菌的重组蛋白PAc的抗原和使用水热法合成的沸石咪唑酯框架-8纳米颗粒(ZIF-8NP)的佐剂制备防龋疫苗。然后,小鼠鼻内给药ZIF-8@PAc疫苗,和免疫反应进行了评估。
结果:ZIF-8NP不仅大大提高了抗原的内化,而且在溶酶体中ZIF-8NP降解后释放PAc蛋白,用于进一步加工和呈递抗原呈递细胞。此外,ZIF-8@PAc诱导更有效的PAc特异性血清IgG和唾液IgA抗体,较高的脾细胞增殖指数,较高水平的细胞因子IL-4,IL-6,IL-10,IL-17A和IFN-γ,体内成熟DC和CD4+记忆T细胞的百分比更高。
结论:ZIF-8NP,作为抗龋齿疫苗佐剂辅助抗原PAc,引发显著有效的免疫反应,帮助进一步预防龋齿。
结论:疫苗免疫疗法是预防和治疗龋齿的一种有吸引力的策略。本研究中ZIF-8@PAc疫苗能显著诱导高水平的免疫应答,这表明预防和治疗龋齿的巨大潜力。
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.
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.
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.
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.
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.