Polyelectrolyte Multilayers Assembled Entirely from Immune Signals on Gold Nanoparticle Templates Promote Antigen-Specific T Cell Response
Polyelectrolyte Multilayers Assembled Entirely from Immune Signals on Gold Nanoparticle Templates Promote Antigen-Specific T Cell Response
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DOI：
10.1021/acsnano.5b02153
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发表时间：
2015-06-01
期刊：
影响因子：
17.1
通讯作者：
Jewell, Christopher M.
中科院分区：
文献类型：
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作者：
Zhang, Peipei;Chiu, Yu-Chieh;Jewell, Christopher M.
允许模块化、有定义地组装免疫信号的材料可以支持新一代合理设计的疫苗，以促进可调节的免疫反应。为了实现这一目标，我们开发了第一种完全由免疫信号构建的聚电解质多层(PEM)涂层。这些免疫膜(IPEM)通过多肽抗原与作为分子佐剂的多阴离子Toll样受体(TLR)激动剂之间的逐步静电相互作用，在金纳米颗粒模板上自组装。IPEM不需要溶剂或混合，可以直接控制疫苗成分的组成和加载，并且可以以任何规模涂覆在基质上。这些薄膜也不需要其他结构成分，消除了许多合成聚合物固有的免疫刺激特性造成的潜在混杂效应。IPEM在金纳米颗粒衬底上的负载是可调的，CryoTEM揭示了涂覆在金芯上的IPEM外壳。这些纳米颗粒被原始树突状细胞(DC)有效地内化，导致激活，选择性地触发TLR信号，并呈递用于组装iPEM的抗原。在共培养中，iPEM驱动抗原特异性T细胞的增殖和效应性细胞因子，而不是与更广泛的炎症相关的细胞因子。与用可溶性抗原和佐剂治疗的小鼠相比，iPEM免疫在1周后促进外周血中高水平的抗原特异性CD8(+)T细胞。这些增强是由于引流淋巴结内DC活化和抗原提呈增加所致。免疫IPEM的小鼠在加强免疫后也表现出强大的召回反应，支持iPEM设计定义明确的疫苗涂层，提供高货物密度并消除合成膜成分的潜力。
Materials that allow modular, defined assembly of immune signals could support a new generation of rationally designed vaccines that promote tunable immune responses. Toward this goal, we have developed the first polyelectrolyte multilayer (PEM) coatings built entirely from immune signals. These immune-PEMs (iPEMs) are self-assembled on gold nanoparticle templates through stepwise electrostatic interactions between peptide antigen and polyanionic toll-like receptor (TLR) agonists that serve as molecular adjuvants. iPEMs do not require solvents or mixing, offer direct control over the composition and loading of vaccine components, and can be coated on substrates at any scale. These films also do not require other structural components, eliminating the potentially confounding effects caused by the inherent immune-stimulatory characteristics of many synthetic polymers. iPEM loading on gold nanoparticle substrates is tunable, and cryoTEM reveals iPEM shells coated on gold cores. These nanoparticles are efficiently internalized by primary dendritic cells (DCs), resulting in activation, selective triggering of TLR signaling, and presentation of the antigens used to assemble iPEMs. In coculture, iPEMs drive antigenspecific T cell proliferation and effector cytokines but not cytokines associated with more generalized inflammation. Compared to mice treated with soluble antigen and adjuvant, iPEM immunization promotes high levels of antigen-specific CD8(+) T cells in peripheral blood after 1 week. These enhancements result from increased DC activation and antigen presentation in draining lymph nodes. iPEM-immunized mice also exhibit a potent recall response after boosting, supporting the potential of iPEMs for designing well-defined vaccine coatings that provide high cargo density and eliminate synthetic film components.