DNA Vaccines

DNA Vaccines
by Laura Putnam

What is a DNA Vaccine?
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A DNA Vaccine is essentially a DNA sequence that can be used as a vaccine. This sequence of DNA comes from an infectious organism such as a bacteria or virus. This sequence codes for a protein that would be created by the infectious organism. The sequence is then injected into a cell of a person, the protein is produced, and an immunity is created against the infectious organism’s proteins, and, essentially, the infectious organism itself. In this way the DNA sequence acts as a vaccine.
How was it discovered?

In the 1980’s, scientists wanted to produce a healing protein for treating a genetic disease
Used naked DNA spliced into plasmids to insert the protein in the person
http://www.roanealliance.org/img/pictures/scientist.jpg
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How was it discovered? (cont.)
Immune system instead responded and destroyed the protein
-The experiment was a failure and the idea was abandoned.
In the 1990’s, scientists realized the process could instead be used to create immunity against proteins from viruses
-They then began to research and develop what are now known as DNA Vaccines.
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How is a DNA Vaccine made?
DNA is isolated
-The DNA sequence which would code for a specific protein is isolated from the genome of the infectious organism.
Eukaryotic promoter and terminator are added
-Bacteria and viruses have different promoters for transcription than do eukaryotes. The eukaryotic cells of a human would not respond to the promoter region from a prokaryote. So, a eukaryotic promoter must be added so that a human cell can begin transcription. A terminator is also necessary so that the exact sequence for the protein is copied and nothing more.
DNA is integrated into a plasmid vector


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How is a DNA Vaccine made? (cont.)
Plasmid is transformed into bacteria
-A bacteria such as E. coli can be used and the plasmid then becomes part of the bacteria’s DNA.
Bacterial growth occurs
-Many more copies of the plasmid containing the infectious organism’s DNA must be produced, so growth of the bacteria is necessary.
Plasmid DNA is purified from the bacteria
-All of the other bacterial DNA and debris are separated from the plasmid with the sequence of DN. This plasmid can now be used to produce the infectious organism’s proteins inside a person.
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How does it work?
Plasmid vectors are injected into muscle cells
-Muscle cells are most commonly used because they are able to take up the plasmids more easily than most other cells.
Cells uptake the plasmid
-The plasmids with the DNA sequence inside them are accepted into the nucleus of the muscle cells.
The gene is expressed inside the cells
-Transcription occurs and the mRNA coding for the infectious organism’s protein is created.
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How does it work? (cont.)
The infectious organism’s protein is produced
-Translation of the mRNA occurs and the protein is now actively being produced in the muscle cells of the person.
The immune system responds to the foreign protein
-The immune system recognizes the proteins are incorrect and attacks them with killer Tcells and memory B cells.
A lasting immune protection is created and maintained
-Memory B cells create antibodies for the specific proteins, and thus the person is protected from the proteins and consequently the infectious organism itself.


vi.wikipedia.org
DNA Vaccines vs. Traditional Vaccines
Uses only the DNA from the infectious organism
Produces the proteins that would be created by the infectious organism
Avoids the risks of using the actual infectious organism
Creates a lasting immune response
Lower cost, easy to manage and use

Uses a weakened form of the actual infectious material
Allows for the infectious organism to actually invade cells in the body
Creates possible risk of the vaccine being fatal
Infectious organism could possibly revert to the wild-type form
Creates an immune response that may vary in effectiveness depending on the person
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DNA Vaccines and HIV
HIV could be prevented using DNA Vaccines
-By isolating the gene for a protein produced by HIV, a DNA Vaccine could be created and immunity for the protein and thus HIV could be established. People would then be able to be immune to HIV.
Many experiments have been done
-Researchers have attempted to create many varying DNA Vaccines, but none have been entirely successful in humans.
Envelope gene
-A specific gene of HIV that could be used to create a DNA Vaccine for HIV.
www.wellesley.edu
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THE QUESTION.
Could a DNA Vaccine using the gene for the envelope protein in HIV create an immune response and lasting protection against the virus?
THE PROCESS.
Isolate the envelope gene from HIV virus
Splice the gene into a plasmid
Transform E. coli with plasmid
Grow culture of E. coli
Purify the plasmid with the envelope gene
Insert into the muscle tissue of a mouse
Examine the immune effects
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THE EFFECTS.
HIV could be prevented
Advancements in technology for creating DNA Vaccines for other infectious organisms could be established
World would be a safer, healthier, happier place
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References
Delude C, Mirvis K, editors. 2000. DNA Vaccines. Your World, Biotechnology & You 9(2):13
Brown, J. Jack’s Bug in the News: What the Heck is a DNA Vaccine? Available from: http://www.people.ku.edu/~jbrown/dnavac.htm Accessed 2006 July 22.
Scuderi, M. 2003 May. What are DNA Vaccines? Available from: http://biology.kenyon.edu/slonc/bio38/scuderi/partii.html Accessed 2006 July 28.
Kumar, S. Immunogenecity of Testing of a Novel Engineered HIV-1 Envelope Gp140 DNA Vaccine Construct [abstract]. Taken from: Pubmed [online database]; Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16848679&query_hl=4&itool=pubmed_docsum Accessed 2006 July 27
Ulmer, J. 2003 Current Protocols in Human Genetics: DNA Vaccination. Taken from John Wiley & Sons. Available from: http://www3.interscience.wiley.com/cgi-bin/mrwhome/104554806/HOME Accessed: 2006 July 27



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