Abstract
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.
Highlights
Dendritic Cells (DCs) play crucial roles in promoting and regulating immune responses, including adaptive immune defences
The high potential of the replicon RNA (RepRNA) delivery for vaccine applications will be elaborated in this review, proposing how progress will lead to enhanced self-amplifying vaccine targeting to DCs
While many studies on DC endocytosis have focused on clathrin-mediated uptake [65], the rapid internalization and acidification associated with this process may lead more to degradation or delivery into Toll-like receptor (TLR)-containing endosomal structures
Summary
Dendritic Cells (DCs) play crucial roles in promoting and regulating immune responses, including adaptive immune defences. There are reports claiming targeting of DCs, many of these do not study interaction with the cells, presuming that an induced immune response reflected DC delivery While this may be the case, it is not guaranteed for nucleic acid delivery. An important property offered by nucleic acid vaccines relates to the initiation of potent immune responses benefitting from vaccines resembling the natural infection of the pathogen in question [3,4]. The high potential of the RepRNA delivery for vaccine applications will be elaborated in this review, proposing how progress will lead to enhanced self-amplifying vaccine targeting to DCs. The nature of the delivery vehicle composition is to provide encapsulation of the RepRNA to protect against RNases, facilitate delivery to DCs and ensure a level of compaction enabling the RepRNA to interact with the ribosomal translation machinery. The surface of the nanoparticulate delivery vehicle may be coated to enhance stability and/or provide a means of enhance targeting of the DCs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
