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

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

Poly(lactic-co-glycolic acid) (PLGA) (Figure 3 ) is a synthetic biodegradable copolymer that has been extensively investigated for the delivery of different therapeutic agents including proteins and nucleic acids [160] . Due to its biocompatibility and excellent safety profile, PLGA is approved by the FDA in various drug delivery systems for human use. Since the degradation rate of PLGA can be adjusted by modifying the molecular weight of the polymer and the lactic acid to glycolic acid ratio, the rate of drug release can also be controlled accordingly. However, the negative charge and hydrophobic nature of PLGA limit its interaction with the negatively charged DNA. Cationic surface modification of PLGA micro/nanoparticles using polycations such as PEI and chitosan can overcome this problem and allow efficient nucleic acids delivery [161] [162] [163] [164] . This strategy has also been applied to the delivery of DNA vaccines. Oster et al. first employed the use of micro-particles consisting PLGA and PEI as DNA vaccine carrier for injection [165] . Later on, Wang et al. reported the use of chitosan coated PLGA nanoparticles to deliver plasmid DNA encoding FMDV (foot-and-mouth disease virus) capsid protein together with IL-6 as mucosal adjuvant for intranasal vaccination [166] . Chitosan coated PLGA nanoparticles were first prepared by emulsion-diffusion-evaporation technique [167] , followed by the incorporation of plasmid DNA to the nanoparticles by simple complexing. The samples were then freeze-dried with mannitol before use. After intranasal administration in guinea pigs and rats, both cellular and humoral immune responses were detected. IL-6 was also found to be an effective mucosal adjuvant which significantly enhanced mucosal and systemic immune responses. More importantly, the vaccines could offer some immune protection to animals against FMDV challenge.