Feature: At the DNA vaccine vanguard

DNA vaccines have been touted for over a decade as a potential game changer in disease control.

However, like many potentially breakthrough technologies that look exciting on paper – from stem cell therapies, to nanotechnology, to personalised medicine – getting them to produce an effective, safe and reliable therapeutic effect in the real world has proven to be a major hurdle.

Yet, if you were dishing out odds on who might be the first to clear that hurdle, Professor Ian Frazer would have to be a front runner. After all, he’s done it before.

Read more about DNA vaccines.

Along with his late colleague, Dr Jian Zhou, Frazer developed the world’s first vaccine for cervical cancer by protecting against human papillomavirus, the virus responsible for the vast majority of the deadly cancers.

Now Frazer has turned his attention towards the tremendous potential of DNA vaccines, with another sexually transmitted disease in his sights: herpes simplex virus 2 (HSV-2).

This stubborn virus has remained defiant to vaccine treatments in the past, but if Frazer’s gambit proves successful, we’ll have not only the world’s first vaccine against the disease, but we could also see the first long-awaited DNA vaccine for humans. The trick will be getting it to work, although preliminary signs are tantalising.

Under the skin

DNA vaccines have been developed and used successfully on animals, with several currently deployed. However, none have yet been approved for human use.

Early human trials for DNA vaccines against viruses such as HIV demonstrated that the technique is well tolerated and safe, but unfortunately the expected levels of immune response weren’t reached. Various labs are now exploring a range of strategies to optimise the immune response in the hope of developing a DNA vaccine that might finally live up to the hype.

Frazer and his team have employed two strategies to boost the performance of their HSV-2 vaccine, both developed through his spinoff biotech, Coridon.

“Our approach started with some research observations made 10 years go about the means by which DNA is translated in human cells, and the fact that the efficiency of transcription of DNA and its translation into proteins is different between different cell types,” says Frazer.

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“That led to technology to improve protein expression from DNA vaccines, which we’ve developed at Coridon. We’ve shown in animal studies that using this technology you can get significantly improved immune responses compared to naked DNA vaccines.

“The second technology that we have come up with enables the production of long lasting cell mediated immune responses to DNA vaccines based on mixing two DNA vaccines together encoding the gene of interest from the virus in both ubiquitinated as well as non-ubiquitinated forms.”

The vaccine will be delivered intradermally for two main reasons. First, this is where the best immune response is produced. “All the interesting immunocytes – the antigen presenting cells – are concentrated in your skin, as the first line of defence against invasion,” says Frazer. As such, you need less antigen to get a strong immune response when it’s injected into the skin.

The other reason is that herpes is predominantly an infection of the skin, so that’s where you want the immune response to occur. “We know that inducing an immune response in skin encourages the trafficking of immune response cells back to skin preferentially, which is, of course, what we’re trying to achieve.”

Animal trials are ongoing, with results of a recent trial in draft for publication at the moment. There is one more round of animal trials on the cards set for early 2011 and this trial will set the scene for human trials, which are expected to kick off in the second half of 2011, regulatory approval permitting, of course.

There are still hurdles yet to leap, but Frazer and his team have a good run up. Should they be successful, we might not only see the first vaccine against a widespread and troublesome disease, but also the world’s first DNA vaccine for humans.

This, in turn, could lead to more DNA vaccines against other curly viruses based on the technology developed by Frazer and Coridon. Makes one wonder: can someone become Australian of the Year twice?

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