The expressions of foreign antigen inserted into plasmid have greatly influenced the world of vaccine. No DNA vaccine has been assigned for human and veterinary use till date but the potential of this vaccine has been tested on animal model which indicate that DNA vaccines are able to elicit response against viral, bacterial and parasitic infection. At present, DNA vaccines for malaria, AIDS, influenza and herpes virus are underway of human trial. In 1990, it has been demonstrated that plasmid DNA can be directly transformed into mouse muscles in vivo without utilizing any specific delivery system. Few studies also revealed that intramuscular inoculation with plasmid DNA encoding reporter gene expressed protein with in muscles cells. These initial studies provide an insight into the beginning of new era of DNA vaccines providing an idea that naked DNA could be delivered in vivo for protein expression. Further, DNA plasmid encoding antigenic protein is now used as DNA vaccine.
DNA vaccine is made up of bacterial expression plasmid which is composed of two units:
(a) Antigenic protein expression unit: It contains specific sequence of promoter followed by antigen encoding DNA sequence and than polyadenylation sequence.
(b) Production unit: It contains all necessary sequence which are required for plasmid amplification in bacteria and for selection purpose like Ori c, selectable marker genes.
Plasmid DNA encoding antigenic protein is injected into muscles of recipient which is followed by the uptake of DNA by muscles cells. Plasmid DNA expresses the antigenic protein leading to both humoral antibody response and a cell mediated response. The DNA integrates into chromosomal DNA or maintains for long period in episomal form. It is found that antigenic protein is expressed by the muscles cells and also by the dendritic cells in the area that take up the plasmid DNA and express antigenic protein. A modern Gene gun method is applied to administer plasmid DNA into muscles cells. In this process plasmid DNA is covered with microscopic gold beads and then delivered these particles through the skin into underlying muscles cells with a gun
Mechanism of action
DNA vaccine elicits both humoral and cell mediated immunity. The transferred DNA is expressed on surface of muscles cells and dendritic cells. The antigenic protein expressed by plasmid DNA is processed through MHC class I pathway by both cell types and antigenic peptide has been expressed on the surface of both cells followed by the stimulation of development of cytotoxic T cells. The antigenic protein encoded by injected DNA is also expressed in form of soluble protein which leads to the processing of antigenic protein through MHC class II pathway. This pathway elicit B- cell immunity which generate antibody and memory B-cell. Finally DNA vaccine is able to elicit significant immunological memory response.
The importance of DNA vaccine lies in fact that the encoded protein is expressed in the host in its natural form so it is very true that immune response is directed to the antigen exactly by the pathogen. For DNA vaccine, single dose delivered to the host is sufficient to elicit immune response .One more advantage of DNA vaccine is introduced with the fact that it does not require refrigeration for handling and storage of plasmid DNA which lowers its cost. The same DNA plasmid can be tailored easily in several ways so that various kind of antigenic protein can be manufactured.
As DNA vaccine is used to encode antigenic protein but many pathogens contain long chain polysaccharide on their outer membrane which acts as antigen. In this case polysaccharide-based subunit vaccines are used for immunization of the host. Some studies have suggested that DNA vaccine elicit autoimmune diseases in mice.
Recently It has been demonstrated that the DNA plasmid encoding antigenic protein against dengue-4 induce strong immune response in mice. The significant progress has been made in the development of DNA vaccine against one of the world's biggest killers - tuberculosis. Various researches have shown that the DNA based vaccines against avian influenza H5N1 causing 'bird flu' found to be capable of providing protection against several strains of H5N1 virus. This vaccines providing immunity against avian influenza virus is currently in phase of clinical trial.
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