Saint-Lu N, Tourdot S, Razafindratsita A, Mascarell L, Berjont N, Chabre H, Louise A, Van Overtvelt L, Moingeon P
Research and Development, Stallergènes SA, Antony, France.
Allergy. 2009 Jul;64(7):1003-13. doi: 10.1111/j.1398-9995.2009.01945.x. Epub 2009 Feb 12.
Sublingual immunotherapy (SLIT) efficacy could be improved by formulations facilitating allergen contact with the oral mucosa and uptake by antigen-presenting cells (APCs).
Two types of chitosan microparticles, differing in size and surface charge, were tested in vitro for their capacity to improve antigen uptake and presentation by murine bone marrow-derived dendritic cells (BMDCs) or purified oral APCs. T-cell priming in cervical lymph nodes (LNs) was assessed by intravenous transfer of carboxyfluorescein diacetate succinimidyl ester-labelled ovalbumin (OVA)-specific CD4+ T cells and flow cytometry analysis. Ovalbumin-sensitized BALB/c mice were treated sublingually with soluble or chitosan-formulated OVA twice a week for 2 months. Airway hyperresponsiveness (AHR), lung inflammation and T-cell responses in cervical and mediastinal LNs were assessed by whole-body plethysmography, lung histology and Cytometric Bead Array technology, respectively.
Only a mucoadhesive (i.e. highly positively charged) and microparticulate form of chitosan enhances OVA uptake, processing and presentation by murine BMDCs and oral APCs. Targeting OVA to dendritic cells with this formulation increases specific T-cell proliferation and IFN-gamma/IL-10 secretion in vitro, as well as T-cell priming in cervical LNs in vivo. Sublingual administration of such chitosan-formulated OVA particles enhances tolerance induction in mice with established asthma, with a dramatic reduction of both AHR, lung inflammation, eosinophil numbers in bronchoalveolar lavages, as well as antigen-specific Th2 responses in mediastinal LNs.
Mucoadhesive chitosan microparticles represent a valid formulation for sublingual allergy vaccines.
通过促进变应原与口腔黏膜接触及抗原呈递细胞（APC）摄取的制剂，可提高舌下免疫疗法（SLIT）的疗效。
测试了两种大小和表面电荷不同的壳聚糖微粒在体外改善小鼠骨髓来源树突状细胞（BMDC）或纯化口腔APC摄取和呈递抗原的能力。通过静脉注射羧基荧光素二乙酸琥珀酰亚胺酯标记的卵清蛋白（OVA）特异性CD4⁺T细胞并进行流式细胞术分析，评估颈部淋巴结（LN）中的T细胞致敏情况。用可溶性或壳聚糖配制的OVA每周两次舌下治疗卵清蛋白致敏的BALB/c小鼠，持续2个月。分别通过全身体积描记法、肺组织学和细胞计数微珠阵列技术评估气道高反应性（AHR）、肺部炎症以及颈部和纵隔LN中的T细胞反应。
只有一种黏膜黏附性（即高正电荷）的微粒形式的壳聚糖可增强小鼠BMDC和口腔APC对OVA的摄取、加工和呈递。用这种制剂将OVA靶向树突状细胞可增加体外特异性T细胞增殖和IFN-γ/IL-10分泌，以及体内颈部LN中的T细胞致敏。舌下给予这种壳聚糖配制的OVA颗粒可增强已患哮喘小鼠的耐受性诱导，显著降低AHR、肺部炎症、支气管肺泡灌洗中的嗜酸性粒细胞数量以及纵隔LN中的抗原特异性Th2反应。
黏膜黏附性壳聚糖微粒是舌下过敏疫苗的一种有效制剂。
