Comparison of antibodies and carbohydrates to target vaccines to human dendritic cells via DC-SIGN
Comparison of antibodies and carbohydrates to target vaccines to human dendritic cells via DC-SIGN
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DOI：
10.1016/j.biomaterials.2012.02.036
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发表时间：
2012-06-01
期刊：
影响因子：
14
通讯作者：
Figdor, Carl G.
中科院分区：
文献类型：
--
作者：
Cruz, Luis J.;Tacken, Paul J.;Figdor, Carl G.
疫苗效力在特异性递送至专职抗原（Ag）呈递细胞如树突状细胞（DC）时得到改善。疫苗组分的抗原性和佐剂性可以通过包封在靶向人DC特异性C型凝集素受体DC-SIGN的纳米颗粒（NP）疫苗载体内来增强。在这里，我们使用两种策略将疫苗组分靶向DC-SIGN：1）碳水化合物作为天然受体配体和2）受体特异性抗体（Ab）。为了确定最佳的靶向策略，我们用DC-SIGN配体Lewis-X（Le（x））、甘露糖基化脂阿拉伯甘露聚糖（ManLAM）、糖基化HIV蛋白gp 120或三种不同的DC-SIGN Ab包被含有MHC I类或II类限制性Ag和TLR配体（TLRL）聚I：C和瑞喹莫特的NP疫苗。虽然，由于其较低的MW，用碳水化合物对NP疫苗进行表面包被导致每个NP的表面分子数高于用Ab包被，但是携带Ab的NP疫苗比携带Le（x）、ManLAM或gp 120的载体更有效地被人DC结合和内化。此外。当与没有TLRL的那些相比时，携带TLRL的NP疫苗触发了DC成熟标志物的显著诱导，而与靶向部分无关。Ab和gp 120介导的靶向诱导同样高水平的促炎细胞因子和增加的MHC I类限制性表位的呈递。相比之下，MHC II类限制性表位的呈递在Ab介导的靶向时比使用gp 120时更有效。Le（x）或ManLAM。从这些发现中，我们得出结论，受体特异性抗体比碳水化合物更有效的DC靶向疫苗接种策略。(c)2012爱思唯尔有限公司保留所有权利。
Vaccine efficacy is improved upon specific delivery to professional antigen (Ag) presenting cells, such as dendritic cells (DCs). Antigenicity and adjuvanticity of vaccine components can be enhanced by encapsulation within nanoparticle (NP) vaccine carriers that are targeted to the human DC-specific C-type lectin receptor DC-SIGN. Here we used two strategies to target vaccines components to DC-SIGN: 1) carbohydrates as natural receptor ligands and 2) receptor-specific antibodies (Abs). To determine the optimal targeting strategy, we coated NP vaccines harboring MHC class I or II-restricted Ags and the TLR ligands (TLRLs) poly I:C and resiquimod with either the DC-SIGN ligands Lewis-X (Le(x)), mannosylated lipoarabinomannan (ManLAM), glycosylated HIV protein gp120, or three distinct DC-SIGN Abs. Although, because of their lower MW, surface coating of NP vaccines with carbohydrates resulted in a higher number of surface molecules per NP than coating with Abs, NP vaccines carrying Abs were more effectively bound and internalized by human DCs than carriers harboring Le(x), ManLAM or gp120. Furthermore. NP vaccines harboring TLRLs triggered significant induction of DC maturation markers when compared to those without TLRLs, irrespective of the targeting moiety. Ab- and gp120-mediated targeting induced equally high levels of proinflammatory cytokines and increased presentation of the MHC class I-restricted epitope. By contrast, presentation of the MHC class II-restricted epitope was more efficient upon Ab-mediated targeting than when using gp120. Le(x) or ManLAM. From these findings we conclude that receptor-specific Abs are more effective than carbohydrates for DC-targeted vaccination strategies. (c) 2012 Elsevier Ltd. All rights reserved.