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The IUP Journal of Biotechnology
Recombinant DNA Vaccines: Present Status and Future Perspective
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Deoxyribonucleic acid (DNA) vaccines are the simplest embodiment of vaccine that rather than consisting of the antigen itself, provide genes encoding the antigen. For several infectious diseases still prevailing throughout the world, there are cell culture vaccines currently being used to control them. With the development of r-DNA technology, there has been a spurt in the development of r-DNA-based vaccines, some of which are working effectively. These have several characteristics like they can be stored at room temperature and do not need cold chain storage; are economic to produce and safe to handle; and are highly effective. DNA vaccines have been developed against hepatitis, rabies, bovine herpes virus, influenza, etc. However, some improvements like vector modification for molecular adjuvant and use of effective adjuvant are needed so that immune responses may be enhanced to combat such infectious diseases effectively.

 
 

During the last 200 years, vaccination has controlled many major diseases and has led to the eradication of many deadly diseases. Vaccines that are used for human beings are mainly of three types: live attenuated microorganisms, inactivated whole microorganisms, or split or subunit preparations. In 1986, the first recombinant subunit vaccine, the hepatitis B surface antigen vaccine, produced in Saccharomyces cerevisiae (Valenzuela et al., 1982), was licensed. First generation vaccines are whole-organism vaccines - either live and weakened or killed forms - (Alarcon et al., 1999), live, attenuated vaccines, such as smallpox and polio vaccines that are able to induce killer T-cell (TC or CTL) responses, helper T-cell (TH) responses, and antibody immunity. However, there is a small risk that attenuated forms of a pathogen can revert to a dangerous form, and may still be able to cause disease in immunocompromised people (such as those with AIDS). While killed vaccines do not have this risk, they cannot generate specific killer T-cell responses, and may not work at all for some diseases. In order to minimize these risks, the so-called second generation vaccines were developed. These are subunit vaccines, consisting of defined protein antigens (such as tetanus or diphtheria toxoid) or recombinant protein components (such as the hepatitis B surface antigen) able to generate TH and antibody responses, but not killer T-cell responses.

DNA vaccines are third generation vaccines, made up of a small, circular piece of bacterial DNA (called a plasmid) that has been genetically engineered to produce one or two specific proteins (antigens) from a microorganism. The DNA vaccine is injected into the cells of the body, where the `inner machinery' of the host cells `reads' the DNA and converts it into pathogenic proteins. Because these proteins are recognized as foreign, they are processed by the host cells and displayed on their surface to alert the immune system, which then triggers a range of immune responses. These DNA vaccines were developed from `failed' gene therapy experiments. The first demonstration of a plasmid-induced immune response was when mice inoculated with a plasmid expressing human growth hormone elicited antibodies, instead of altering growth (Tang et al., 1992).

 
 
 

Biotechnology Journal, DNA vaccines, Recombinant, Adjuvant, attenuated microorganisms, subunit vaccine, Saccharomyces cerevisiae, Valenzuela, polio vaccines, CTL, hepatitis B surface antigen, third generation vaccines, pathogenic proteins, surface to alert the immune system, hormone elicited antibodies, strategies for vaccine development, pathogenic agent