通过合成纳米颗粒将自我扩增复制子RNA疫苗递送至树突状细胞
Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles.
作者信息
McCullough Kenneth C, Milona Panagiota, Thomann-Harwood Lisa, Démoulins Thomas, Englezou Pavlos, Suter Rolf, Ruggli Nicolas
机构信息
Institute of Virology and Immunology, CH-3147 Mittelhaeusern, Switzerland.
出版信息
Vaccines (Basel). 2014 Oct 16;2(4):735-54. doi: 10.3390/vaccines2040735.
Dendritic cells (DC) play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for RNA-interference has proven successful, the methodologies are identical for RNA vaccines, which require delivery to RNA translation sites. Delivery of mRNA has benefitted from application of cationic entities; these offer value following endocytosis of RNA, when cationic or amphipathic properties can promote endocytic vesicle membrane perturbation to facilitate cytosolic translocation. The present review presents how such advances are being applied to the delivery of a new form of RNA vaccine, replicons (RepRNA) carrying inserted foreign genes of interest encoding vaccine antigens. Approaches have been developed for delivery to DCs, leading to the translation of the RepRNA and encoded vaccine antigens both in vitro and in vivo. Potential mechanisms favouring efficient delivery leading to translation are discussed with respect to the DC endocytic machinery, showing the importance of cytosolic translocation from acidifying endocytic structures. The review relates the DC endocytic pathways to immune response induction, and the potential advantages for these self-replicating RNA vaccines in the near future.
树突状细胞(DC)在决定疫苗递送对免疫防御发育和调节的功效方面发挥着重要作用。这使得DC成为疫苗递送的重要靶点,尤其是RNA疫苗。虽然将干扰RNA寡核苷酸递送至RNA干扰的合适细胞内位点已被证明是成功的,但这些方法与RNA疫苗相同,RNA疫苗需要递送至RNA翻译位点。mRNA的递送受益于阳离子实体的应用;当阳离子或两亲性特性可促进内吞小泡膜扰动以促进胞质转位时,这些在RNA内吞后具有价值。本综述介绍了这些进展如何应用于新型RNA疫苗——携带插入的编码疫苗抗原的外源目的基因的复制子(RepRNA)的递送。已经开发出将其递送至DC的方法,从而在体外和体内实现RepRNA和编码疫苗抗原的翻译。关于DC内吞机制,讨论了有利于有效递送导致翻译的潜在机制,显示了从酸化内吞结构进行胞质转位的重要性。该综述将DC内吞途径与免疫反应诱导相关联,并阐述了这些自我复制RNA疫苗在不久的将来的潜在优势。