Yu You-Bo, Liu Ying, Li Sha, Yang Xiao-Yan, Guo Zhong
Center for Biological Science and Technology, Guangdong Zhuhai-Macao Joint Biotech Laboratory, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai, China; Zhuhai Key Laboratory of Basic and Applied Research in Chinese Medicine, College of Bioengineering, Zhuhai Campus of Zunyi Medical 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.
J Dent. 2023 Mar;130:104413. doi: 10.1016/j.jdent.2023.104413. Epub 2023 Jan 10.
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.
变形链球菌是龋齿的主要致病菌，其蛋白抗原（PAc）已被用作抗龋疫苗。此外，几种融合蛋白或与佐剂结合的PAc被用作抗龋疫苗，以改善PAc相对较弱的免疫原性。然而，目前尚无具有良好生物相容性、优异生物降解性或高抗原负载性能的基于纳米颗粒的佐剂用于抗龋疫苗。本研究旨在制备一种创新的基于纳米颗粒的抗龋疫苗，并在体外和体内评估该疫苗引发的免疫反应。
在本研究中，利用水热法合成的沸石咪唑酯骨架-8纳米颗粒（ZIF-8 NPs）作为佐剂，与变形链球菌重组蛋白PAc抗原制备抗龋疫苗。然后，通过鼻腔给予小鼠ZIF-8@PAc疫苗，并评估免疫反应。
ZIF-8 NPs不仅极大地提高了抗原的内化，而且在溶酶体中ZIF-8 NPs降解后释放出PAc蛋白，以供抗原呈递细胞进一步加工和呈递。此外，ZIF-8@PAc在体内诱导产生了明显更强的PAc特异性血清IgG和唾液IgA抗体、更高的脾细胞增殖指数、更高水平的细胞因子IL-4、IL-6、IL-10、IL-17A和IFN-γ，以及更高比例的成熟DCs和CD4记忆T细胞。
ZIF-8 NPs作为抗龋疫苗佐剂辅助抗原PAc，引发了明显有效的免疫反应，有助于进一步预防龋齿。
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疫苗可诱导产生显著高水平的免疫反应，这表明其在龋齿预防和治疗方面具有巨大潜力。
