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

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

Chitosan (Figure 3) is a natural polysaccharide that has been frequently studied for drug delivery. It is derived from chitin which is found abundant in crustacean. It is biodegradable and biocompatible with low toxicity [150, 151] . The properties of chitosan can be tuned by changing its molecular weight and degree of deacetylation. Because of its cationic nature, chitosan has strong binding affinity with nucleic acids, making it a suitable candidate for DNA delivery agent. In addition, chitosan and its derivatives are found to display strong mucoadhesive property, making them particularly suitable to facilitate intranasal delivery [152] [153] [154] . Moreover, chitosan was also reported to have an immunostimulating effect, such as increasing the accumulation and activation of macrophages, promoting resistance to infections by cytokines, and enhancing cytotoxic T cell response [155, 156] . A number of studies have described the use of chitosan nanoparticles to deliver DNA vaccine formulation for intranasal administration. Kumar et al. reported the exploitation of chitosan nanoparticles to deliver DNA vaccine against acute respiratory syncytial virus (RSV) infection [156] . A cocktail of plasmid DNA encoding a number of RSV antigens was used to complex with chitosan to form nanoparticles. Following the nasal vaccination in mice, high levels of serum IgG and mucosal IgA antibodies, as well as cytotoxic T cells responses were induced. There was also an elevated lung-specific production of IFN-γ with antiviral action. A single dose of DNA vaccine was able to decrease the RSV titers by 100-fold on primary infection. Similar study was performed by another group who described the use of chitosan nanoparticles to deliver plasmid DNA encoding a T cell epitope from the M2 protein of RSV [157] . It was found that intranasal administration of the formulation in mice induced specific cytotoxic T cell response that was comparable to those induced via intradermal immunization. Following RSV challenge of the nasal immunized mice, the virus load in lungs was significantly reduced.