Revision as of 00:02, 14 September 2011

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. (more on Wikipedia)

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 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.

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-<h1>What are DNA Vaccines?</h1>
+<h1>Introduction to DNA Vaccines</h1>
-DNA vaccines are made up of small genetically engineered plasmids, each containing a DNA sequence which codes for antigenic protein of a pathogen. This form of immunization, also known as ''third generation'' vaccination, is a novel technique used to efficiently stimulate innate and humoral (antibody) immune responses to protein antigens.
+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.
-PICTURE
+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!
-<h1>How are DNA vaccines different from other vaccines?</h1>
+DNA vaccines work beautifully in stages to promote an immune response to infection as well as develop immunity:
-''First generation'' vaccines are whole-organism vaccines – either live and attenuated, or killed forms. Live, attenuated vaccines, such as smallpox and polio vaccines, are able to induce both innate and humoral immune responses (killer T-cell response, helper T-cell response and antibody immunity)[2]. However, there is a small risk that attenuated forms of a pathogen can revert to the wild-type virulent form, and may still be able to cause disease in immunocompromised people (such as those with AIDS)[3]. While killed vaccines have the advantage of non-infectivity and therefore relative safety, they cannot generate specific killer T-cell responses (lower immunogenicity and consequently need for several doses) and may not work at all for some diseases[4].
+# 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.
+<ol start="4">
+<li>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.</li>
+<li>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. <html><a href="http://en.wikipedia.org/wiki/B_cell#Activation_of_B_cells" target="_blank">(more on Wikipedia)</a></html></li>
+</ol>
+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.
-In order to minimise these risks, so-called ''second generation'' vaccines were developed. These are subunit vaccines, consisting of defined protein antigens such as tetanus or diphtheria toxoid (inactivated bacterial toxins that can induce protective antibody)[5] or recombinant protein compounds such as the hepatitis B surface antigen. These, too, are able to generate T-helper cell and antibody responses, but not killer T-cell responses.
+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/TheWayForward|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.
-Firstly, the vaccine DNA is delivered into the cells of the body where the “inner machinery” of the host cells transcribes the DNA to mRNA. Then the DNA is translated to form pathogenic proteins[1]. Because these proteins are recognised as foreign, when they are processed by the host cells and displayed on their surface, the immune system is alerted, which then triggers a range of immune responses of the host against the gene delivered antigen. In this way, DNA vaccine provides immunity.
 </div>
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Team:UCL London/Medicine/DNAVaccines

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Revision as of 00:02, 14 September 2011

Introduction to DNA Vaccines