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

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

Currently, there are at least two approved liposomal vaccine formulations on the market for antigen delivery, including Inflexal ® V (influenza vaccine) and Epaxal ® (hepatitis A vaccine). Both formulations employed the virosomes technology (Figure 4) , in which the viral proteins are bound to the surface of a liposome in an array, similar to what is seen on viral particles [171] . The idea is to create a safe viral-like particle that can induce strong protective immune response. Similar technology could be applied to DNA vaccines to improve immunogenicity. In fact, liposomes on their own could elicit immune response even in the absence of other antigens. It has been demonstrated by Lay et al. that DOTIM (octadecenoyloxy-ethyl-heptadecenyl-3-hydroxyethyl imidazolinium chloride)/cholesterol cationic liposome-DNA complexes (JVRS-100), in which an empty plasmid DNA vector was incorporated, were able to induce high levels of antibody and T cell immunity in mice and non-human primates [174] . Since lipid composition, particle size, surface charge and DNA entrapment efficiency of the liposomes can affect their immunogenicity and potency, these parameters must be carefully characterized and controlled. The major limitation of liposome as DNA vaccine carrier is long-term stability, as lyophilization of liposomes may not be always possible [171] . [175] . Plasmid DNA encoding Ag85A was complexed with the lipids. Following intranasal immunization in mice, naked DNA was completely ineffective, probably due to the degradation of the DNA by mucosal nuclease. The lipid-DNA formulation was capable of inducing a weak cell-mediated immune response, and no humoral immune response was detected. The co-lipid intranasal formulation was compared with another cationic lipid formulation, Vaxfectin, which was used for intramuscular administration. It was found that the intramuscular formulation was able to induce a better immune response. However, combining intranasal and intramuscular administrations resulted in stronger immune responses in the lungs. Considerable improvement is needed to further develop the formulation for intranasal use.