Why are DNA vaccines the way forward?

Problems with current vaccines

Live attenuated vaccines

• Insufficient attenuation
• Reversion to wild type
• Administration to immunodeficient patient
• Persistent infection
• Contamination by other viruses
• Fetal damage

Non-living vaccines

• Contamination by toxins or chemicals
• Allergic reactions
• Autoimmunity

Such problems can be mitigated in DNA vaccines through stringent clinical evaluations and the valuable support of translational research coming from molecular biology, genetics, and biotechnology.

RANDOM PICTURE

Promising returns from DNA vaccines

DNA third generation vaccines can easily surpass most if not all problems that current vaccines face. The goal of mounting an effective and holistic immune response[2] can be accomplished through identifying the DNA sequence coding for a unique antigenic protein associated with the pathogen, such that subsequent to host cell transfection with the innocuous DNA vaccine, both MHC Class I and MHC Class II antigen processing pathways will be undertaken, and this triggers both the innate (helper T-cell) and humoral (antibody) immune responses. DNA vaccines have proven to be effective in stimulating antibody responses to attack infectious diseases as they enter the body, before they can infect cells, therefore acting as a preventive vaccine. They are also efficient at generating T-cell responses that may kill targeted cancerous cells or cells infected by the targeted virus of bacteria. Therefore, DNA vaccines may there also be used a therapeutic to treat existing disease. This capability provides the potential to treat chronic infectious diseases such as HIV and hepatitis C virus, as well as the possibility to develop therapeutic cancer vaccines.

There are numerous important infectious diseases for which a satisfactory vaccine is not yet available, but by adopting and building on this DNA vaccine platform, those previously inconceivable vaccines are now a possibility[3].

TABLE

DNA vaccine technology provides the opportunity to design sophisticated, multi-antigen vaccines and/or vaccines based on conserved genes and antigens that are common to the evolved strains of a pathogen, e.g. the potential exists to develop a universal influenza vaccine to protect against both seasonal influenza strains as well as new influenza strains that cannot be known in advance and which present pandemic risk, such as new strains of avian influenza or the Mexican H1N1 influenza[4]. It can potentially be developed from concept to FDA approval in eight to 10 years, rather than as much as 20 years that it took to develop, for example, the chickenpox vaccine. Plasmids are fairly stable at room temperature, again in contrast to a number of live vaccines whose storage and global delivery are complicated by the need to keep the vaccines cold. This synergises well with the fact that DNA vaccines can be readily and cost effectively manufactured using off-the-shelf, well-proven fermentation technology. We will witness the advent of an universal panacea within our lifetime, should ample funding and manpower be allocated to research and development in this field.

By harnessing the phenomenon of supercoiling and introducing it to DNA vaccines to make them more compact and robust, hence raising host cell transfection rate and product stability, our team project E.coili has demonstrated DNA vaccine’s potential as a credible, viable, and scalable platform that can spawn more novel therapeutic strategies in years to come, not to mention extending the boundaries of immunotherapy research. Also worth noting also is that our team project aims to raise public awareness of DNA vaccines, and we are doing that through public engagement. We would like to communicate to policymakers and members of the public who have vested interests in third generation vaccines that this technology is safer than current viral vector vaccines; our supercoiling of plasmid DNA has made them compact enough now to transfect cells just as easily as the viral vector. Given the choice between DNA vaccines or viral vaccines, it is easy to make the choice: DNA vaccines as they are innocuous beneficial to global biosafety and wards against bioterrorism[5].

Analysis and conclusion[6]

The ongoing technological developments, such as formulations and electroporation, may provide the needed increase in immunogenicity by the combinations of increased antigen production and additional immunologic responses due to the inflammation caused by the formulations and electroporation themselves.

However, the concerns about the chromosomal integration seen in a safety study of electroporation, despite the differences in devices and electrical settings, mean that this technology needs careful evaluation for humans, whose longer lifespan than a food animal may change the risk:benefit ratio. Nevertheless, these various delivery technologies merit continued development and evaluation.

DNA vaccines have begun to show their promise by the licensure of animal products and several clinical trials in which the immunologic results appear to be more potent than earlier trials. The robustness of the technology and ease with which experimental constructs could be made enabled those of us in the field to select systems for experiments and product development perhaps too easily, going for the home run experiments and product development pathways. Because of the many experiments and the insights gained into the immunologic mechanisms, the field has made remarkable progress in the development of a vaccine platform as well as illuminating aspects of immune responses to disease.

The clear advantages of this technology for rapid responses to emerging diseases, for resource-poor settings, and for the diversity of applications ranging from prophylaxis to therapy and from immune activation to immune modulation will best be developed by our careful clear-eyed assessment of all the disease-specific issues, immune mechanisms, and technologies in order to enable DNA vaccines to accomplish their potential for benefitting human and animal health.