Stahl Monika, Holzinger Jonas, Bülow Sigrid, Goepferich Achim M
Department of Pharmaceutical Technology, University of Regensburg, Regensburg, Germany.
Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.
Nanomedicine. 2022 Jun;42:102545. doi: 10.1016/j.nano.2022.102545. Epub 2022 Mar 11.
Nanoparticles hold great potential as vaccine carriers due to their highly versatile structure and the possibility to influence intracellular trafficking and antigen presentation by their design. In this study, we developed a nanoparticulate system with a new enzyme-triggered antigen release mechanism. For this novel approach, nanoparticle and model antigen ovalbumin were linked with a substrate of the early endosomal protease cathepsin S. This construct enabled the transfer of antigens delivered to bone marrow-derived dendritic cells from the endo-lysosomal compartments in the cytosol. Consecutively, our particles enhanced cross-presentation on dendritic cells and subsequently promoted a stronger activation of CD8 T cells. Our findings suggest that enzyme-triggered antigen release allows the endosomal escape of the antigen, leading to increased MHC-I presentation. Since T cell immunity is central for the control of viral infections and cancer, this release mechanism offers a promising approach for the development of both prophylactic and therapeutic vaccines.
由于其高度通用的结构以及通过设计影响细胞内运输和抗原呈递的可能性，纳米颗粒作为疫苗载体具有巨大潜力。在本研究中，我们开发了一种具有新型酶触发抗原释放机制的纳米颗粒系统。对于这种新方法，纳米颗粒与模型抗原卵清蛋白与早期内体蛋白酶组织蛋白酶S的底物相连。这种构建体能够将递送至骨髓来源树突状细胞的抗原从胞质溶胶中的内溶酶体区室转移出来。随后，我们的颗粒增强了树突状细胞上的交叉呈递，并随后促进了CD8 T细胞的更强激活。我们的研究结果表明，酶触发的抗原释放允许抗原从内体逃逸，导致MHC-I呈递增加。由于T细胞免疫对于控制病毒感染和癌症至关重要，这种释放机制为预防性和治疗性疫苗的开发提供了一种有前景的方法。
