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Team:UCL London/Medicine/DNAVaccines
From 2011.igem.org
Introduction to DNA Vaccines
DNA vaccines are made up of small plasmids1. Each plasmid has been genetically modified by inserting an identified DNA sequence which codes for an antigenic protein2 of a pathogen. This form of immunisation is termed third generation vaccination, and is a novel technique used to stimulate an effective and holistic immune response in the inoculated patient.
For DNA vaccines to work, they have to be delivered into the patient’s body, just like any other vaccine. There are various delivery methods, with saline intramuscular (IM) injection and gene gun delivery being the most popular. Whilst IM injection requires no special delivery mechanism unlike the gene gun, it uses up a relatively large amount of plasmid DNA, normally100 – 200 micrograms. With the gene gun delivery method, as little as 16 nanograms of plasmid DNA are required – almost a difference by 1000 fold!
DNA vaccines work beautifully in stages to promote an immune response to infection as well as develop immunity:
- Plasmid DNA (pDNA) enter host’s cell. This is called transfection.
- It then enters the nucleus of the cell and uses the ‘inner machinery’ to replicate itself just like ordinary genomic DNA.
- Replication ends with the translation of the DNA sequence embedded in the plasmid to a protein molecule. In this case, it is the specific antigenic protein that we want as our final product.
The specific antigenic protein can be processed in two different ways, and each is responsible for a type of immune response: innate (non-specific) response and humoral (antibody, specific) response.
- Innate response: the antigenic protein fragments (may be broken down after protein synthesis) or peptides will be displayed on the transfected cell. This is carried out by MHC class I molecules3 which displays the antigen in its groove. When a white blood cell called T-killer cell locates and binds to this antigenic complex (the pathogenic antigen and MHC class I complex), it is primed. This induces the T-killer cell to multiply and kill the bound cell and others displaying those same peptides in the same way.
- Humoral response: the antigenic protein is released out of the host cell and white blood cells called B-cells will locate and bind with these antigens. Once this happens, the B-cell will proliferate and produce progeny (offspring) which secretes antibody molecules that 4opsonises the pathogen and marks it for the T-killer cell for 5phagocytosis. In actuality, several preliminary steps must occur before such a response can arise.
Immunity is developed in both the innate and humoral arm of the immune system. This happens everytime during proliferation. Not every progeny becomes an activated B-cell or killer-T cell. Some will become memory B cells and memory T-killer cells, which stay on to protect against future infection.
Whilst there are public concerns and scepticism regarding health risks of DNA vaccines, results from toxicology studies have so far demonstrated that DNA vaccines are both safe and well tolerated.
Our mission: synergising this applied research with translational biomedical research DNA vaccines offer to the world [Team:UCL_London/Medicine/DNAVaccines/WayForward|promising returns], and this is the reason why we have chosen this project – developing a toolkit for the industrial manufacturing of supercoiled plasmid DNA. This will enable a widespread adoption of pDNA based technologies, most relevantly DNA vaccines, the future of immunization. Our manufacturing project translates to a strong impact on the global health sector.
