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

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

In recent years, there has been an increasing concern that vaccination in general may induce harmful systemic inflammation, which may lead to increase of cardiovascular risk [45] [46] [47] [48] [49] . DNA vaccine is still considered as a relatively new approach to vaccination but its potential to induce systemic inflammation must not be overlooked. It was reported that little or no local inflammatory infiltration was observed at the DNA vaccine injection site, especially after the acute effects of the vaccination have disappeared [9] . The first clinical trial of a DNA-based vaccine for HIV-1 infection was published in 1998 in 15 asymptomatic HIV-infected patients who were not using antiviral drugs. The immunization was well tolerated with neither local, systemic reaction nor laboratory abnormalities were detected after three doses of vaccines [38] . In addition, no patient developed anti-DNA antibody or muscle enzyme elevations. No consistent change of CD4 + or CD8 + lymphocyte counts occurred. Another early experiment conducted on pigs showed that electroporation of DNA vaccines was more efficient in enhancing immune response, but also stimulated inflammatory response and accompanying cellular infiltration, whereas the conventional intramuscular injection of DNA vaccines only showed low gene expression and low inflammatory cell infiltration [50] . It was suggested that improved antigen presentation was one of the possible mechanisms by which increased inflammatory cell infiltration may enhance immune responses to DNA vaccines delivered with electroporation. However, the long-term safety effect was not investigated.