Feature: Inside DNA vaccines

It was a classic case of scientific serendipity. In the 1990s, researchers were investigating the possibilities of gene therapy and they found, much to their surprise, that naked DNA injected directly into the host didn’t do what they expected it to.

Instead of combining with the host’s DNA, it provoked an immune response against the protein encoded by the implanted gene. While that proved a setback for that particular line of gene therapy, it opened up an intriguing possibility: DNA-based vaccines.

Instead of attempting to produce an immune response against a foreign protein by isolating it and presenting that to the immune system, you could simply inject DNA that encoded that protein, and let the body’s cellular machinery do the heavy lifting for you.

This is done by isolating one or more proteins unique to the pathogen being targeted. These would then be inserted into a plasmid and then injected under the skin or into the muscle.

The plasmid is then absorbed by a cell, which manufactures the protein and presents it on its surface along with a major histocompatibility complex protein. The plasmid can also be picked up directly by an antigen presenting cell, and then the immune system swings into action.

Furthermore, unlike conventional vaccines, the body doesn’t only produce antibodies against the invader, but also engages a cell-mediated response by calling in the T-cells. “Philosophically it’s a different approach from the more conventional vaccines, which have been targeted at producing antibody first and foremost,” says Professor Ian Frazer.

“We’re taking a belt and braces approach: make antibody to mop up most of the virus, and make a cell-mediated immune response to kill off cells that happen to get infected.

“And then keep that cell-mediated immune response going over time, so if virus latency should be established, it stays latent and doesn’t come out to create attacks of disease later down the track.”

Because of its dual nature, the vaccine should also have both a prophylactic as well as therapeutic effect, so it can potentially lend a benefit to both non-infected and infected individuals.

It may even have a therapeutic effect on herpes simplex virus 1, although that’s not the focus of Frazer’s current effort to develop a vaccine for herpes simplex type 2.

This feature appeared in the January/February 2011 issue of Australian Life Scientist. To subscribe to the magazine, go here.