Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines.
Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines.
复制标题
DOI：
10.1016/j.biomaterials.2015.11.009
复制
发表时间：
2016
期刊：
影响因子：
14
通讯作者：
Lei Zhang;Zhanzhuang Zeng;Chaohua Hu;S. Bellis;Wendi Yang;Yintao Su;Xinyan Zhang;Yunkun Wu
中科院分区：
文献类型：
--
作者：
Lei Zhang;Zhanzhuang Zeng;Chaohua Hu;S. Bellis;Wendi Yang;Yintao Su;Xinyan Zhang;Yunkun Wu
结构简单的传统口服疫苗在刺激有效免疫方面面临障碍。在这里，我们描述了一种具有智能相-过渡屏蔽层的口服疫苗，聚[(甲基丙烯酸甲酯)-co-(丙烯酸甲酯)-co-(甲基丙烯酸)]-聚(d，L-丙交酯-乙交酯)(PMMMA-PLGA)，它可以保护胃肠道中的抗原，实现大肠的靶向免疫。以B组链球菌(GBS)表面免疫原性蛋白(SIP)为抗原，口服PMMMA-PLGA(PTRBL)/TRX-SIP纳米颗粒对免疫系统相对简单的罗非鱼具有较强的免疫刺激作用。该疫苗成功地预防了无乳链球菌，这是一种威胁人类健康的世界性重要病原体，通过受感染的鱼在水中传播。口服PTRBL/TRX-SIP疫苗后，罗非鱼产生了较高水平的SIP特异性抗体，并显示出持久的免疫保护作用。接种疫苗的罗非鱼100%不受GBS感染，而未接种疫苗的对照组和接种TRX-SIP的对照组在初次接种后的最初5个月内的感染率分别为100%或60%。体内实验证明，FITC标记的重组抗原TRX-SIP定位于结肠、脾和肾脏，这是发动免疫反应的关键部位。我们的结果表明，与纳米颗粒的大小相比，更有可能的是PMMMA中的羧基电离产生的负电荷斥力保护了纳米颗粒不被小肠上皮细胞摄取。该系统解决了胃肠道损伤对抗原的挑战，更重要的是，为口服疫苗提供了一种新的途径。
Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly(d,l-lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group BStreptococcus(GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia, an animal with a relatively simple immune system. The vaccine succeeded in protecting againstStreptococcus agalactiae, a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination.