基于壳聚糖的纳米系统作为肺炎球菌疫苗传递平台。
A chitosan-based nanosystem as pneumococcal vaccine delivery platform.
机构信息
Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, A Coruña, Spain.
Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, A Coruña, Spain.
出版信息
Drug Deliv Transl Res. 2021 Apr;11(2):581-597. doi: 10.1007/s13346-021-00928-3. Epub 2021 Mar 2.
Chitosan-based nanosystems have been described as interesting tools for antigen delivery and for enhancing the immunogenicity of nasally administered vaccines. As a possible vaccine delivery method, the chemical conjugation of chitosan nanocapsules with the Streptococcus pneumoniae cell membrane protein PsaA (pneumococcal surface adhesin A) is suggested here. The antigen PsaA, common to all pneumococcus serotypes, is expected to improve its uptake by immune cells and to activate specific T cells, generating an adaptive immune response against pneumococcus. With this aim, chitosan nanocapsules with thiol-maleimide conjugation between the polymer (chitosan) and the antigen (PsaA) were designed to enable the surface presentation of PsaA for immune cell recognition. Spherical-shaped particles, with a size of 266 ± 32 nm, positive charge of +30 ± 1 mV, and good stability profiles in simulated nasal fluids (up to 24 h) were achieved. PsaA association rates were three times higher compared with nanocapsules without covalent polymer-protein conjugation. Cytotoxicity studies in cell culture media showed non-toxic effect under 150 µg/mL concentration of nanocapsules, and subsequent studies on the maturation of immature dendritic cells in the presence of antigen-conjugated nanocapsules displayed peripheral blood mononuclear cell activation and lymphocyte differentiation after their presentation by dendritic cells. Secretion of TNFα following exposure to nanocapsules and the ability of nanocapsules to activate CD4 and CD8 T lymphocytes had also been studied. Antigen loaded nanocarrier uptake and presentation by professional presenting cells.
壳聚糖纳米系统已被描述为用于抗原传递和增强鼻内给予疫苗的免疫原性的有趣工具。作为一种可能的疫苗递送方法,建议将壳聚糖纳米胶囊与肺炎球菌细胞膜蛋白 PsaA(肺炎球菌表面黏附素 A)进行化学缀合。PsaA 是所有肺炎球菌血清型共有的抗原,有望增强其被免疫细胞摄取的能力,并激活特异性 T 细胞,从而对肺炎球菌产生适应性免疫反应。为此,设计了具有聚合物(壳聚糖)和抗原(PsaA)之间硫醇-马来酰亚胺缀合的壳聚糖纳米胶囊,以使 PsaA 能够进行表面呈现以进行免疫细胞识别。实现了粒径为 266 ± 32nm、表面正电荷为 +30 ± 1mV 的球形颗粒,在模拟鼻液中具有良好的稳定性(长达 24 小时)。与没有共价聚合物-蛋白缀合的纳米胶囊相比,PsaA 的结合率提高了三倍。在细胞培养基中的细胞毒性研究表明,纳米胶囊在浓度为 150μg/mL 以下时无毒性作用,随后在存在抗原缀合纳米胶囊的情况下研究未成熟树突状细胞的成熟情况,显示出树突状细胞呈递后外周血单核细胞的活化和淋巴细胞分化。还研究了 TNFα 的分泌以及纳米胶囊激活 CD4 和 CD8 T 淋巴细胞的能力。载有抗原的纳米载体被专业呈递细胞摄取和呈递。