The effect of the physical form of poly(lactic-co-glycolic acid) carriers on the humoral immune response to co-delivered antigen
The effect of the physical form of poly(lactic-co-glycolic acid) carriers on the humoral immune response to co-delivered antigen
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DOI：
10.1016/j.biomaterials.2004.08.023
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发表时间：
2005-06-01
期刊：
影响因子：
14
通讯作者：
Babensee, JE
中科院分区：
文献类型：
--
作者：
Bennewitz, NL;Babensee, JE
将模型脱落抗原卵清蛋白(OVA)以微粒(MP)或支架(SC)的形式引入到聚乳酸-乙醇酸(PLGA)聚合物生物材料载体中。然后将这些结合了抗原的聚合物生物材料载体注射或植入小鼠体内，通过跟踪OVA特异性免疫球蛋白的浓度和酶联免疫吸附试验(ELISA)来评估产生的对受控释放的OVA的依赖时间的全身体液免疫反应。为了评估不同形式的载体(MP和SC)对免疫应答的增强程度，两种载体的聚合物和OVA的总量以及OVA的释放率保持不变。植入伴有组织损伤的PLGA SC释放的OVA的体液免疫反应水平较高且持续，而注射微创传递的PLGA MP释放相同数量的聚合物和OVA时，体液免疫应答水平较低且短暂。这种免疫反应主要依赖Th2辅助T细胞，尽管对于强佐剂、CFA和PLGA SC携带者来说，Th2和Th1应答都有贡献。这些结果暗示，由于组织损伤，植入支架会产生危险信号，从而使系统产生增强的免疫反应。(C)2004爱思唯尔有限公司。保留所有权利。
A model shed antigen, ovalbumin (OVA), was incorporated into polymeric biomaterial carriers made of poly(lactic-co-glycolic acid) (PLGA) in the form of microparticles (MP) or scaffolds (SC). These polymeric biomaterial carrier vehicles with incorporated antigen were then injected or implanted into mice and the resulting time-dependent systemic humoral immune response towards the controlled released OVA was assessed by following the OVA-specific IgG concentration and isotypes using ELISA. To assess the differential level of enhancement of the immune response depending on the form of carrier vehicle (MP vs. SC), the total amount of polymer and OVA delivered was kept constant as well as the release rate of OVA for both carrier vehicles. The level of the humoral immune response was higher and sustained for OVA released from PLGA SC which were implanted with associated tissue damage, and lower and transient when the same amount of polymer and OVA were delivered from PLGA MP, which were minimally invasively delivered by injection. This immune response was primarily Th2 helper T cell-dependent, although for the strong adjuvant, CFA, and PLGA SC carriers there was both a Th2 and Th1 response contribution. These results implicate 'danger signals' associated with the implantation of the scaffolds due to tissue injury which primed the system for an enhanced immune response. (C) 2004 Elsevier Ltd. All rights reserved.