The Shock and Awe Approach to Delivering DNA Vaccines

Science Not Fiction
By Jeremy Jacquot
Aug 9, 2010 10:32 PMNov 20, 2019 2:27 AM


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A patient receiving a flu shot. In the not too distant future, the phrase "shooting up" could take on a whole new meaning. At least if the U.S. Army has its way. Wired's Danger Room blog reported a few days ago that the military is seeking bids for a high-tech form of vaccination that could be delivered quickly and efficiently to a large number of troops in the heat of battle. More specifically, the Pentagon wants a DNA vaccine that can be administered via a literal shot to the arm—and a jolt of electricity. All without causing too much "discomfort" to the patient, of course. Suffice it to say that this futuristic-sounding vaccine would be a far cry from what you and I received as children. As last year's swine flu epidemic made painfully clear, our current methods of vaccine development, which have remained essentially unchanged for decades, are woefully outdated. The vaccines take too long—upwards of seven months—to produce, are easily prone to failure if not prepared correctly and, in many cases, lose their potency after only a year. These failings have helped draw attention to DNA-based vaccines, cocktails of genetically engineered plasmids which offer the promise of inducing a stronger, and more targeted, immune response. Where regular vaccines are slow to develop and hard to combine, DNA vaccines can be made relatively quickly and mixed together to ward off multiple pathogens at once. They are also generally safer to produce and administer, more durable and can be scaled more easily. Like other vaccines, however, they are still primarily injected into muscles and thus suffer from the same inefficiency problems. Because the DNA is not injected directly into the host cells but into the spaces between them (the "intracellular spaces"), the vaccine first needs to be taken up before the cells can mount a robust response and pump out the necessary disease-fighting proteins. The two main alternatives cited in the Army's solicitation are gene guns and intramuscular electroporation. The first gene gun was designed in the 1980s by a Cornell University scientist as a tool with which to transform plant cells by blasting them with microscopic DNA-coated gold or tungsten beads carried on a powerful whiff of helium gas. Gene guns have since focused their crosshairs on animals and humans alike, particularly after the Army recently embraced them as their vaccine delivery method of choice. The main downside is that it can only deliver small quantities of DNA, not the two or more vaccines at a time that the Army wants. Intramuscular electroporation, which improves vaccine uptake by temporarily opening pores in their membranes through short bursts of electricity, can be used to supply sufficient amounts of DNA, but it comes at a cost: pain. So what ideal device would the Army like?

The optimal vaccination strategy would capitalize on the efficiency of electroporation, eliminate the discomfort associated with intramuscular injection, and be useful for simultaneous delivery of two or more DNA vaccines. A minimal successful outcome would provide effective delivery with reduced discomfort for one DNA vaccine.

For the moment, electroporation seems to be the method of choice among the companies operating in this burgeoning field. Inovio, a Pennsylvania-based startup that has emerged as one of the field's dominant players, claims that its electroporation system can boost cellular uptake of a vaccine 1,000-fold or more. The company employs a handheld needle-electrode applicator tethered to an electric pulse generator to inject the vaccine into skin or muscle and deliver a few short zaps of electricity to jostle the cells into taking it up. Unlike most such electroporation systems, Inovio claims its own is relatively painless—"tolerable without anesthetic." But it's important to bear in mind that while DNA vaccines are making concrete progress, they still have quite a ways to go before they supplant conventional vaccines. (Plasmid purification, in particular, remains a challenge.) With any luck, the Army will have found its desired device by the time the first DNA vaccines hit the production line.

Image: alvi2047/Flickr

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