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球形金纳米粒子在免疫中的应用前景。

Prospects for the use of spherical gold nanoparticles in immunization.

机构信息

Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, Saratov, Russian Federation.

Saratov State Vavilov Agrarian University, Saratov, Russian Federation.

出版信息

Appl Microbiol Biotechnol. 2019 Jan;103(1):437-447. doi: 10.1007/s00253-018-9476-5. Epub 2018 Nov 6.

Abstract

Recent years have seen extremely fast development of new viral nanovaccines and diagnostic agents using nanostructures prepared by biological and chemical synthesis. We used spherical gold nanoparticles (average diameter, 15 nm) as a platform for the antigen for swine transmissible gastroenteritis virus (TGEV). The literature data demonstrate that immunization of animals with the TGEV antigen coupled to gold nanoparticles (GNPs) not only activates antigen-presenting cells but also increases the proliferative activity of splenic lymphoid (antibody-forming) cells. The contents of γ-IFN, IL-1β, and IL-6 in animals immunized with GNP-antigen conjugates were found to be higher than those in intact animals or in animals given the antigen alone. The increased concentration of IL-1β in the immunized animals directly correlated with the activity of macrophages and stimulated B cells, which produce this cytokine when activated. The increased concentration of IL-6 indicates that the injected preparations are stimulatory to cellular immunity. Immunization with the TGEV antigen conjugated to GNPs as a carrier activates the respiratory activity of lymphoid cells and peritoneal macrophages, which is directly related to their transforming activity and to the activation of antibody generation. Furthermore, the use of this conjugate allows marked improvement of the structure of the animals' immune organs and restores the morphological-functional state of these organs. The microanatomical changes (increased number of follicles) indicate the activation of the B-dependent zone of the spleen and, consequently, the development of a humoral-type immunological reaction. The degradative processes observed in the animals immunized with TGEV antigen alone are evidence of weak resistance to pathogen attack. These results can be used to develop vaccines against this infection by employing TGEV antigen coupled to gold nanoparticles as a carrier.

摘要

近年来,使用生物和化学合成制备的纳米结构,新型病毒纳米疫苗和诊断试剂得到了飞速发展。我们以 15nm 平均直径的球形金纳米粒子(gold nanoparticles,GNPs)作为猪传染性胃肠炎病毒(transmissible gastroenteritis virus,TGEV)抗原的载体。文献数据表明,用 TGEV 抗原偶联的金纳米粒子(GNPs)免疫动物,不仅能激活抗原呈递细胞,而且能增加脾淋巴细胞(产生抗体)的增殖活性。与完整动物或单独给予抗原的动物相比,用 GNP-抗原缀合物免疫的动物体内 γ-干扰素(IFN)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的含量更高。免疫动物中 IL-1β 的浓度升高与巨噬细胞的活性直接相关,巨噬细胞被激活后会产生这种细胞因子。IL-6 浓度的升高表明,所注射的制剂对细胞免疫有刺激作用。用 TGEV 抗原偶联的 GNPs 作为载体进行免疫可激活淋巴细胞和腹腔巨噬细胞的呼吸活性,这与它们的转化活性和抗体生成的激活直接相关。此外,使用这种缀合物可显著改善动物免疫器官的结构,并恢复这些器官的形态和功能状态。微观解剖学的变化(滤泡数量增加)表明了脾脏 B 依赖区的激活,从而导致了体液型免疫反应的发展。单独用 TGEV 抗原免疫的动物中观察到的降解过程表明,它们对病原体攻击的抵抗力较弱。这些结果可用于开发针对该感染的疫苗,方法是将 TGEV 抗原偶联到金纳米粒子作为载体上。

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