Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines

Self-amplifying replicon RNA (RepRNA) are highly RNase-sensitive and inefficiently enter dendritic cells (DCs), an absolute requirement for vaccine design. Therefore, polyethylenimine (PEI)-based polyplexes were assessed for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid. Polyplex-formulation protected the RepRNA and promoted an efficient intracellular delivery to DCs, leading to RepRNA translation. This efficacy was confirmed in vivo - polyplex-RepRNA complexes induced both humoral and cellular immune responses. This work demonstrates for the first time PEI-based polyplexes as efficient delivery vehicles of large, self-amplifying RepRNA vaccines.318