DNA Vaccines for Flu and AIDS

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Production of flu shots for H1N1 lagged far behind schedule because the viruses didn't grow as fast as expected.

“They don't grow any faster if you yell at them!” as one spokesman said. It takes months to produce a batch of flu shots, so the manufacturers have to guess which strains are going to be prevalent in each year's seasonal flu outbreaks. Exceptional strains, such as the H1N1 (swine) flu and the H5N1 (bird) flu variants, create special challenges because the flu can spread so widely before vaccines are ready for mass distribution.

That's one motivation for DNA vaccines. Viruses are unable to reproduce outside of living cells, and they are much too complicated for conventional chemical synthesis. However, the immune system does not require the entire virus particle in order to produce antibodies against it. Proteins are the primary targets of the white blood cells that recognize foreign invaders. Viruses typically come with a protein coat that can be identified and attacked.

Researchers have developed techniques to produce tiny loops of DNA, called plasmids, containing one or more genes coding for specific proteins. Under favorable conditions, these plasmids can enter cells of humans or animals and cause the cells to produce a viral protein. That protein is then released from the cell and flagged by the immune system. Thus, a DNA plasmid vaccine can immunize the patient with just the protein coat from a virus, which is produced by the patient's own cells.

Live virus vaccines carry some risk of infecting the patient, if the live virus is not sufficiently weakened. DNA plasmid vaccines eliminate this possibility completely. In addition, the plasmids themselves do not induce an immune response.

There are many technical challenges to this approach. Plasmid HIV vaccines so far have been unsuccessful because of low efficiencies in getting the plamids into the cells, and low rates of viral protein production. A study called the STEP trial was halted in summer 2009 because the vaccine appeared to paradoxically increase the risk of HIV infection, compared to the placebo group. Researchers are still analyzing the data to see what went wrong and what progress can be made.

More encouraging results have been seen in veterinary DNA vaccines. A plasmid based therapy for fetal loss in pigs has already been licensed for use. Other disorders targeted in animals include:
1. West Nile virus (horses)
2. Infectious hematopoietic necrosis virus (farmed salmon)
3. Melanoma (dogs).
The dog melanoma treatment has been shown to increase survival time of dogs with advanced melanoma by sixfold, compared with untreated dogs. This offers great hope for cancer researchers to extend the results to humans.

Clinical trials are underway for influenza plasmid vaccines. Check with your doctor if you would like to participate.

Reference:

Matthew P. Morrow and David B. Weiner, “DNA Drugs Come of Age”, Scientific American, July 2010, p. 49-53.

Linda Fugate is a scientist and writer in Austin, Texas. She has a Ph.D. in Physics and an M.S. in Macromolecular Science and Engineering. Her background includes academic and industrial research in materials science. She currently writes song lyrics and health articles.

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