不同粒径口蹄疫病毒样颗粒-ZIF-8复合物诱导小鼠的体液免疫效果分析

Evaluation of the humoral immunity in mice induced by foot-and-mouth disease virus-like particles-ZIF-8 complexes with different sizes

摘要:

为进一步提高口蹄疫(foot-and-mouth disease, FMD)病毒样颗粒(virus-like particles, VLPs)疫苗的免疫效果，本研究采用仿生矿化方法，将Zn²⁺和2-甲基咪唑按照不同浓度配比制备了不同粒径的FMDV VLPs-沸石咪唑骨架-8 (zeolitic imidazolate framework-8, ZIF-8)复合物，以探究尺寸效应对免疫效果的影响。结果显示，成功制备出3种不同粒径的FMDV VLPs-ZIF-8，粒径分别约为70、100、1 000 nm。细胞毒性和组织病理学试验表明，3种复合物均具有良好的生物安全性。小鼠免疫试验表明，3种复合物均能明显提高中和抗体和特异性抗体水平，并且随着复合物体积的减小，其免疫效果也随之增强。本研究表明，ZIF-8包封FMDV VLPs可显著增强其免疫效果，且具有尺寸依赖性。

关键词:沸石咪唑骨架-8;口蹄疫病毒样颗粒;佐剂;尺寸效应

Abstract:

To further enhance the immune effect of the foot-and-mouth disease (FMD) virus-like particles (VLPs) vaccine, this study prepared FMDV VLPs-zeolitic imidazolate (framework-8, ZIF-8) complexes with different particle sizes. We used a biomimetic mineralization method with Zn²⁺ and 2-methylimidazole in different concentration ratios to investigate the effect of size on the immunization effect. The results showed that FMDV VLPs-ZIF-8 with three different sizes were successfully prepared, with an approximate size of 70 nm, 100 nm, and 1 000 nm, respectively. Cytotoxicity and animal toxicity tests showed that all three complexes exhibited excellent biological safety. Immunization tests in mice showed that all three complexes enhanced the titers of neutralizing and specific antibodies, and their immune effects improved as the size of the complexes decreased. This study showed that ZIF-8 encapsulation of FMDV VLPs significantly enhanced their immunogenic effect in a size-dependent manner.

Key words:zeolitic imidazolate framework-8 (ZIF-8);foot-and-mouth disease virus-like particles (FMDV VLPs);adjuvants;size effect