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Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles.

McCullough KC, Milona P, Thomann-Harwood L, Démoulins T, Englezou P, Suter R, Ruggli N - Vaccines (Basel) (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology and Immunology, CH-3147 Mittelhaeusern, Switzerland. kenneth.mccullough@vetsuisse.unibe.ch.

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.

No MeSH data available.


Related in: MedlinePlus

The basic RepRNA construct ensures efficient translation of the encoded vaccine antigen of interest, as well as replication of the replicon. Insertion of an internal ribosomal entry site (IRES) from, for example, EMC virus ensures that translation of the proteins for replication continues after translation of the vaccine antigen of interest.
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vaccines-02-00735-f002: The basic RepRNA construct ensures efficient translation of the encoded vaccine antigen of interest, as well as replication of the replicon. Insertion of an internal ribosomal entry site (IRES) from, for example, EMC virus ensures that translation of the proteins for replication continues after translation of the vaccine antigen of interest.

Mentions: RepRNA is derived from defective virus genomes (Figure 2). While RepRNA efficiently replicates and translates its encoded antigens, the defect prevents production of progeny virus [1,6,7,8,9,10]. This provides biosafe products, which in turn are readily engineered for carrying genes encoding vaccine antigens (Figure 2). A most important characteristic of RepRNA, offering a major advantage over inactivated or otherwise non-replicating vaccines, is the mimicking of virus replication in the sense of providing several rounds of replication; this increases mRNA templates and therefore enhanced antigen provision beyond the quantity possibly by conventional protein-based vaccines. This affords characteristics associated with efficient induction of both humoral immunity and cytotoxic cell-mediated immunity (CMI).


Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles.

McCullough KC, Milona P, Thomann-Harwood L, Démoulins T, Englezou P, Suter R, Ruggli N - Vaccines (Basel) (2014)

The basic RepRNA construct ensures efficient translation of the encoded vaccine antigen of interest, as well as replication of the replicon. Insertion of an internal ribosomal entry site (IRES) from, for example, EMC virus ensures that translation of the proteins for replication continues after translation of the vaccine antigen of interest.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494254&req=5

vaccines-02-00735-f002: The basic RepRNA construct ensures efficient translation of the encoded vaccine antigen of interest, as well as replication of the replicon. Insertion of an internal ribosomal entry site (IRES) from, for example, EMC virus ensures that translation of the proteins for replication continues after translation of the vaccine antigen of interest.
Mentions: RepRNA is derived from defective virus genomes (Figure 2). While RepRNA efficiently replicates and translates its encoded antigens, the defect prevents production of progeny virus [1,6,7,8,9,10]. This provides biosafe products, which in turn are readily engineered for carrying genes encoding vaccine antigens (Figure 2). A most important characteristic of RepRNA, offering a major advantage over inactivated or otherwise non-replicating vaccines, is the mimicking of virus replication in the sense of providing several rounds of replication; this increases mRNA templates and therefore enhanced antigen provision beyond the quantity possibly by conventional protein-based vaccines. This affords characteristics associated with efficient induction of both humoral immunity and cytotoxic cell-mediated immunity (CMI).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology and Immunology, CH-3147 Mittelhaeusern, Switzerland. kenneth.mccullough@vetsuisse.unibe.ch.

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.

No MeSH data available.


Related in: MedlinePlus