Tuberculosis (TB) is the leading cause of death from a single infectious microorganism and Bacillus Calmette Guerin (BCG), the only authorized vaccine, does not confer protection against pulmonary TB. Based on the hypothesis that mucosal protection could help to prevent the infection at the site of entrance, the objective of this work was to develop an intranasal vaccine against Mycobacterium tuberculosis (Mtb), the microorganism that causes TB. Our approach consisted of the use of polymeric nanocapsules (NCs) with an oily core and a polymer shell made of chitosan (CS) or inulin/polyarginine (INU/pArg). The immunostimulant Imiquimod, a Toll-like receptor-7 (TLR-7) agonist, was encapsulated in the oily core and a fusion protein, formed by two antigens of Mtb, was absorbed either onto the NC surface (CS:Ag and INU:pArg:Ag) or between two polymer layers (INU:Ag:pArg) in order to assess the influence of the antigen positioning on the immune response. Although CS NCs were more immunostimulant than the INU/pArg NCs in vitro, the in vivo experiments showed that INU:pArg:Ag NCs were the only prototype inducing an adequate immunoglobulin A (IgA) response. Moreover, a previous immunization with BCG increased the immune response for CS NCs but, conversely, decreased for INU/pArg NCs. Further optimization of the antigen and the vaccination regime could provide an efficacious vaccine, using the INU:pArg:Ag NC prototype as nanocarrier.

中文翻译：

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用于结核分枝杆菌鼻内疫苗接种的聚合物纳米胶囊的设计：聚合物外壳和抗原定位的影响。


结核病 (TB) 是单一传染性微生物导致死亡的主要原因，而卡介苗 (BCG) 作为唯一获得批准的疫苗，并不能提供针对肺结核的保护作用。基于粘膜保护有助于预防入口部位感染的假设，这项工作的目的是开发一种针对结核分枝杆菌（Mtb） （引起结核病的微生物）的鼻内疫苗。我们的方法包括使用具有油核和由壳聚糖 (CS) 或菊粉/聚精氨酸 (INU/pArg) 制成的聚合物壳的聚合物纳米胶囊 (NC)。免疫刺激剂咪喹莫特是一种 Toll 样受体 7 (TLR-7) 激动剂，被封装在油性核心中，而由两种 Mtb 抗原形成的融合蛋白则被吸附到 NC 表面（CS:Ag 和 INU: pArg:Ag) 或两个聚合物层 (INU:Ag:pArg) 之间，以评估抗原定位对免疫反应的影响。尽管CS NCs在体外比INU/pArg NCs具有更强的免疫刺激作用，但体内实验表明INU:pArg:Ag NCs是唯一能诱导足够的免疫球蛋白A (IgA)反应的原型。此外，先前的 BCG 免疫增加了 CS NC 的免疫反应，但相反，减少了 INU/pArg NC 的免疫反应。使用 INU:pArg:Ag NC 原型作为纳米载体，进一步优化抗原和疫苗接种方案可以提供有效的疫苗。