Caetano Liliana Aranha, Figueiredo Lara, Almeida António J, Gonçalves L M D
a Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy , University of Lisbon , Lisbon , Portugal.
b Department of Ciências e Tecnologias Laboratoriais e Saúde Comunitária, ESTeSL - Escola Superior de Tecnologia da Saúde de Lisboa , Instituto Politécnico de Lisboa , Lisbon , Portugal.
J Microencapsul. 2017 Mar;34(2):203-217. doi: 10.1080/02652048.2017.1316325. Epub 2017 Apr 19.
The aim of this study was to develop a novel BCG-loaded chitosan vaccine with high association efficiency which can afford efficient interaction with APC and elicit local and Th1-type-specific immune response after intranasal administration. Chitosan-suspended BCG and BCG-loaded chitosan-alginate microparticles were prepared by ionotropic gelation. Interaction with APC was evaluated by fluorescence microscopy using rBCG-GFP. Specific immune responses were evaluated following intranasal immunisation of mice. Cellular uptake was approximately two-fold higher for chitosan-suspended BCG. A single dose of BCG-loaded microparticles or chitosan-suspended BCG by intranasal route improved Th1-type response compared with subcutaneous BCG. Chitosan-suspended BCG originated the highest mucosal response in the lungs by intranasal route. These positive results indicate that the proposed approach of whole live BCG microencapsulation in chitosan-alginate for intranasal immunisation was successful in allowing efficient interaction with APC, while improving the cellular immune response, which is of interest for local immunisation against tuberculosis.
本研究的目的是开发一种具有高结合效率的新型负载卡介苗的壳聚糖疫苗,该疫苗能够与抗原呈递细胞(APC)进行有效相互作用,并在鼻内给药后引发局部和Th1型特异性免疫反应。通过离子凝胶法制备了壳聚糖悬浮卡介苗和负载卡介苗的壳聚糖-海藻酸盐微粒。使用重组卡介苗-绿色荧光蛋白(rBCG-GFP)通过荧光显微镜评估与APC的相互作用。在对小鼠进行鼻内免疫后评估特异性免疫反应。壳聚糖悬浮卡介苗的细胞摄取量大约高两倍。与皮下注射卡介苗相比,单剂量鼻内途径的负载卡介苗微粒或壳聚糖悬浮卡介苗可改善Th1型反应。壳聚糖悬浮卡介苗通过鼻内途径在肺部引发最高的黏膜反应。这些积极结果表明,所提出的将完整活卡介苗微囊化于壳聚糖-海藻酸盐中用于鼻内免疫的方法成功实现了与APC的有效相互作用,同时改善了细胞免疫反应,这对于局部抗结核免疫具有重要意义。