The effect of antigen encapsulation in chitosan particles on uptake, activation and presentation by antigen presenting cells.
The effect of antigen encapsulation in chitosan particles on uptake, activation and presentation by antigen presenting cells.
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DOI：
10.1016/j.biomaterials.2012.11.066
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发表时间：
2013-03
期刊：
影响因子：
14
通讯作者：
Zaharoff, David A.
中科院分区：
文献类型：
--
作者：
Koppolu, Bhanuprasanth;Zaharoff, David A.
正在探索基于颗粒的疫苗递送系统以增强针对安全但免疫原性差的多肽抗原的抗原特异性免疫。壳聚糖是一种很有前途的抗原包封和递送生物材料，因为它能够在温和的水性条件下形成纳米颗粒和微米颗粒，从而保持负载多肽的抗原性。在这项研究中，壳聚糖封装的抗原呈递细胞（APC）的抗原摄取，激活和呈递的影响进行了探讨。以异硫氰酸荧光素标记的牛血清白蛋白（FITC-BSA）和卵清蛋白（OVA）为模型蛋白，采用沉淀凝聚法将其包埋在壳聚糖颗粒中，包埋率> 89%。操作配制条件以产生具有离散标称尺寸（300 nm、1μm和3μm）的抗原包封的壳聚糖颗粒（AgCP）。树突状细胞和巨噬细胞对AgCP的摄取依赖于颗粒大小、抗原浓度和暴露时间。流式细胞仪分析显示，AgCP的摄取增强了APC表面活化标记物的上调，并增加了促炎细胞因子的释放。最后，抗原特异性T细胞表现出更高的增殖反应时，刺激与AgCP激活的APC与可溶性抗原。这些数据表明，壳聚糖颗粒中的抗原包封增强了APC的摄取、活化和呈递。
Particle-based vaccine delivery systems are under exploration to enhance antigen-specific immunity against safe but poorly immunogenic polypeptide antigens. Chitosan is a promising biomaterial for antigen encapsulation and delivery due to its ability to form nano- and microparticles in mild aqueous conditions thus preserving the antigenicity of loaded polypeptides. In this study, the influence of chitosan encapsulation on antigen uptake, activation and presentation by antigen presenting cells (APCs) is explored. Fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) and ovalbumin (OVA) were used as model protein antigens and encapsulated in chitosan particles via precipitation-coacervation at loading efficiencies >89%. Formulation conditions were manipulated to create antigen-encapsulated chitosan particles (AgCPs) with discrete nominal sizes (300nm, 1µm, and 3µm). Uptake of AgCPs by dendritic cells and macrophages was found to be dependent on particle size, antigen concentration and exposure time. Flow cytometry analysis revealed that uptake of AgCPs enhanced upregulation of surface activation markers on APCs and increased the release of pro-inflammatory cytokines. Lastly, antigen-specific T cells exhibited higher proliferative responses when stimulated with APCs activated with AgCPs versus soluble antigen. These data suggest that encapsulation of antigens in chitosan particles enhances uptake, activation and presentation by APCs.
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DOI：
10.1038/nrd1176
发表时间：
2003-09
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
O'Hagan DT;Valiante NM
通讯作者：
Valiante NM
影响因子：
5.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Brinster, Carine
影响因子：
5.8
作者：
Gan, Quan;Wang, Tao
通讯作者：
Wang, Tao