ABSTRACT
Compared to other conventional vaccine technologies, such as adjuvanted protein, recombinant vector, and attenuated pathogens, the concept of DNA vaccination is relatively simple. A specific gene of interest from a particular pathogen is cloned into a plasmid containing a powerful promoter active in eukaryotic cells and, upon injection into vaccinees, the antigen is produced in situ. The expressed protein is then processed and presented to the immune system by the MHC class-1 restricted pathway for CTL induction, the MHC class-II restricted pathway for the induction of helper T (Th) cell responses and to B cells for the induction of antibodies. It has been known for quite some time that direct inoculation of linear or plasmid DNA could result in gene expression in vivo [1,2]. The power of this technology for inducing potent immune responses and its potential for vaccine application was demonstrated by Tang et al. [3], Ulmer et al. [4], Fynan et al. [5], Wang et al. [6], and many others in different animal models. Using the gene gun to deliver plasmid DNA into the skin of mice, Tang et al. [3] demonstrated the induction of antibody responses. Ulmer et al. [4] first demonstrated the induction of CTL responses and proof of principle for protective efficacy of a DNA vaccine encoding influenza nucleoprotein (NP). Specifically, these animals were protected from both morbidity and mortality upon lethal challenge with a heterosubtypic strain of influenza A virus. While substantial antibody responses were also generated against NP, protection was demonstrated to be cell mediated [4]. Later that same year, DNA vaccine studies were extended to other diseases such as HIV [6], rabies virus [7], and hepatitis B [8]. These early studies established several important features of DNA vaccines: 1) both antibody and cellular immune responses can be induced; 2) immune responses can be induced by different routes of immunization (intramuscular and epidermal); and 3) it is possible to express foreign genes in vivo with proper structure and conforma tion, as judged by the induction of neutralizing antibodies. Since then, DNA immunization has been used successfully to induce immune responses in animal species
from mice to humans with DNA encoding antigens from various sources such as HIV [9-14], herpes simplex virus-1 (HSV-1) [15-18], HSV-2 [19-21], rabies [7,22-24], hepatitis C [25,26], tuberculosis [27-30], malaria [31-34], mycoplasma [35], toxoplasma [36-40], rotavirus [4143], Ebola virus [44-46], and many others. In addition to infectious diseases, the DNA vaccine strategy has been shown to be potentially a very powerful tool in animal models of allergy, asthma, and cancer.
