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

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

The field of DNA vaccination is developing rapidly. DNA vaccines are currently approved for veterinary use against various infectious diseases [5] [6] [7] [8] . However, the results in clinical trials have been less encouraging. DNA vaccines are generally safe and well tolerated in human, but the immune response is often too low to offer sufficient protection [5, [9] [10] [11] . In early studies, DNA vaccines alone were not able to generate T cell responses at a magnitude that was enough to protect against difficult diseases in humans [12, 13] . Recent attempts still failed to overcome this problem. A plasmid pTHr DNA HIV-1 vaccine candidate evaluation in phase I clinical trials on healthy volunteers showed that it had weak immunogenicity in human. No significant HIV-1-specific cell-mediated immune response difference was found between vaccine recipients and placebo recipients, in addition to no HIV specific antibody production [14] . Another phase I trial of HIV vaccine using DNA prime-virus vector vaccine boost strategy on healthy volunteers was proved effective in eliciting T-cell responses but incapable of inducing neutralizing antibody activities [15] . In 2012, a human HIV-1 gag DNA vaccine with or without interleukin (IL)-12 and/or IL-15 plasmid cytokine adjuvant was reported to produce poor cellular immunogenicity with no vaccine-induced anti-gag humoral immune responses on healthy volunteers, which contrasted with the previous findings in macaques [11] . Several strategies have been introduced to optimize DNA vaccines [16] . One of them is to enhance the DNA delivery efficiency, which is the focus of this review. DNA delivery efficiency is dependent on the administration route and the delivery system used. Mucosal surfaces are attractive sites of vaccine administration against infectious diseases as they are the portals of entry for many pathogens. Vaccination at the mucosal sites where pathogens initiate infections can be more efficacious than parenteral administration as invading pathogens may be neutralized at the front lines before generating any systemic effect. In particular, intranasal vaccine has been extensively investigated in recent years. Vaccination at nasal mucosa can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissue (NALT) where large amounts of local lymphocytes are present. Furthermore, intranasal delivery is a needle-free, non-invasive route of administration with the possibility of self-administration. Intranasal DNA vaccination has become a promising approach in offering immune protection against various pathogens that affect the respiratory system including tuberculosis, coronavirus infection, influenza and respiratory syncytial virus (RSV). In this article, the current developments of DNA vaccine delivery systems that are specifically designed for intranasal administration against respiratory infectious diseases are discussed in detail.