Team:UCL London/Medicine/DNAVaccines/Plasmids


Plasmid Technology

Plasmid based DNA vaccines for human consumption are currently in clinical trials. Advantages behind this manufacturing method are: DNA plasmids are facile to manipulate and hence rapid to construct. They are also relatively easy to manufacture, and the process is generic, in contrast to the complicated processes needed for vaccines such as attenuated viruses meaning it produces cheaper vaccines than the egg-based method. One can make the constructs without having to even work with the live pathogen, since the genes encoding the antigens can be constructed chemically rather than by needing to derive them from the live virulent organism. Because the DNA vaccines consist simply of a plasmid without other antigens, such as a viral or bacterial vector would have, no issues related to prior-exposure to the pathogen arise. The constructs can easily be made to code for proteins that have been modified to eliminate regions that have either functions or immunologic properties that are deleterious, thus improving on the proteins and antigens as delivered by the wild type agent in terms of both immunogenicity and safety.

The problem with the plasmid technology method is that the transfection of the DNA into the cells is not optimal, especially in larger animals.[17] So far, human DNA vaccines are still in clinical trials. Despite ample toxicology evidence indicating that DNA vaccines and their delivery methods are safe in preclinical trials (please refer to toxicology section), we cannot rule out the possibility that side effects may still be felt by the patient during clinical trials. There are speculations that extended immunostimulation will lead to acute and/or chronic inflammation and that may lead to destruction of normal tissues[18]. It may also generate autoimmune diseases in the patient such as autoimmune myositis and anti-DNA antibodies[19], which compromise vaccine efficacy and develop tolerance within the host. Last but not least, despite numerous major genetic breakthroughs achieved in recent years, we are still sometimes dealing with the unknown with genetic vaccines. There is the slightest chance that modification to a DNA sequence can cascade into a geneticist’s worst nightmare of insertional mutagenesis, chromosome instability, turning on oncogenes and turning off tumor suppressor genes.