Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, Germany.
Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria.
Front Immunol. 2021 Oct 21;12:732298. doi: 10.3389/fimmu.2021.732298. eCollection 2021.
Immune modulating therapies and vaccines are in high demand, not least to the recent global spread of SARS-CoV2. To achieve efficient activation of the immune system, professional antigen presenting cells have proven to be key coordinators of such responses. Especially targeted approaches, actively directing antigens to specialized dendritic cells, promise to be more effective and accompanied by reduced payload due to less off-target effects. Although antibody and glycan-based targeting of receptors on dendritic cells have been employed, these are often expensive and time-consuming to manufacture or lack sufficient specificity. Thus, we applied a small-molecule ligand that specifically binds Langerin, a hallmark receptor on Langerhans cells, conjugated to a model protein antigen. microneedle injection, this construct was intradermally administered into intact human skin explants, selectively loading Langerhans cells in the epidermis. The ligand-mediated cellular uptake outpaces protein degradation resulting in intact antigen delivery. Due to the pivotal role of Langerhans cells in induction of immune responses, this approach of antigen-targeting of tissue-resident immune cells offers a novel way to deliver highly effective vaccines with minimally invasive administration.
免疫调节疗法和疫苗的需求很高，尤其是最近 SARS-CoV2 在全球范围内的传播。为了有效激活免疫系统，专业的抗原呈递细胞已被证明是此类反应的关键协调者。特别是靶向方法，主动将抗原引导至专门的树突状细胞，有望更有效，并且由于脱靶效应较少，载物量减少。尽管已经使用基于抗体和聚糖的树突状细胞受体靶向，但这些方法通常制造昂贵且耗时，或者特异性不足。因此，我们应用了一种小分子配体，该配体特异性结合朗格汉斯细胞上的标志性受体 Langerin，并将其与模型蛋白抗原偶联。通过微针注射，将该构建体皮内给药到完整的人皮肤外植体中，选择性地在表皮中加载朗格汉斯细胞。配体介导的细胞摄取超过了蛋白降解，从而实现了完整的抗原传递。由于朗格汉斯细胞在诱导免疫反应中的关键作用，这种针对组织驻留免疫细胞的抗原靶向方法为使用微创管理提供高效疫苗提供了一种新方法。
