Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

Xu, Yingying; Yuen, Pak-Wai; Lam, Jenny Ka-Wing

Polyethylenimine (PEI) (Figure 3) is one of the early generation polymers being investigated for gene delivery. It has high transfection efficiency and is frequently regarded as the gold-standard of non-viral gene delivery vectors. PEI has high pH buffering capacity, which allows its cargo to escape from endosomal entrapment via a mechanism known as "proton sponge hypothesis" [146] . Transfection efficiency of PEI depends on its molecular weight and the level of branching. Shim et al. described the use of a simple method to prepare PEI (25 kDa)-DNA complexes for vaccine delivery [147] . Plasmid DNA encoding SARS-CoV spike protein without transmembrane domain was employed in the study. Mice that were immunized intranasally with the PEI-DNA vaccines produced significantly higher systemic spike protein specific IgG and mucosal secretory IgA in the lung compared to those immunized with naked DNA. Furthermore, cellular immune responses were detected with an improvement of specific T cell responses. In another study, Torrieri-Dramard et al. demonstrated the utilization of PEI (in vivo-jetPEI ® ) as DNA vaccine carrier for intranasal administration [148] . Plasmid DNA encoding HA from influenza A viruses was used. The intranasal administration of the PEI/DNA vaccines induced cellular and humoral immune response capable of providing protective immunity against a divergent virus of H5N1 subtype in mice. The protection could be further improved by including the plasmid DNA encoding NA.