Researchers are preparing to test a vaccine to thwart the spread of a deadly contagious cancer in an iconic Australian marsupial, the Tasmanian devil (Sarcophilus harrisii).
Devil facial tumour disease (DFTD) has killed up to 80% of Tasmanian devils since it first emerged in Tasmania — the large island southeast of mainland Australia — three decades ago, raising fears that the feisty marsupials could go extinct.
Devil facial tumour cells spread from animal to animal and are able to slip past the devil’s immune system because they produce few of the molecules called major histocompatibility complex class I (MHC-1) proteins, which the immune system uses to recognize harmful invaders. The vaccine targets one of the two forms of the disease and aims to make the tumour cells more visible to the immune system. “It’s an exciting step forward,” says Hannah Siddle, a geneticist at the University of Queensland in Brisbane, Australia.
Andrew Flies, a wildlife immunologist at the University of Tasmania in Hobart, and his team were inspired to develop their DFTD vaccine by the release of COVID-19 vaccines from AstraZeneca and Johnson & Johnson, which use a similar technology. The vaccines’ success “gave us the confidence to move ahead”, says Flies.
Like those COVID-19 vaccines, the DFTD vaccine is carried into cells by an adenovirus — a virus that normally causes mild cold-like symptoms in humans — that has been genetically modified so it cannot multiply or cause disease. Such viruses are useful delivery vehicles for vaccines, because they have evolved to break into cells.
After the DFTD vaccine enters devil cells, it causes them to produce proteins that exist in tumour cells, but not most healthy cells. These proteins train the immune system to recognize tumour cells as originating outside the body. If a tumour does invade, the immune system’s memory of the vaccine proteins will encourage the tumour’s cells to express MHC-1, making it easier for the immune system to detect them and mount an attack, says Flies.
The vaccine focuses on devil facial tumour 1 (DFT1), which was first detected in 1996 and has spread to most of Tasmania. Another version of the disease, called devil facial tumour 2, emerged in 2014, and is restricted to a small area in the southeast of the island. The cancers are spread when devils bite each other during brawls over food or mates, and result in debilitating tumours on the face and neck, and inside the mouth.
“These directly transmissible tumours are so rare in nature,” says Hamish McCallum, an infectious-disease ecologist at Griffith University in Gold Coast, Australia. “To have two in the same species is utterly extraordinary and I don’t think anybody’s got a really good handle on what has caused that.”
Devil of a job
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On 14 June, Australia’s Office of the Gene Technology Regulator (OGTR) issued a licence authorizing Flies and his colleagues to test the DFT1 vaccine on 22 healthy captive Tasmanian devils. Only devils that are free from DFTD and no longer have any remnants of the experimental vaccine in their systems will be released into the wild after the trial.
“The pieces of the puzzle for making this vaccine have fallen into place in the past few years,” says Flies. “But we don’t know if it will work until we try.”
The first phase of the trial will assess whether the vaccine is safe and elicits an immune response. If that goes to plan, the researchers will expose vaccinated and unvaccinated devils to the disease to investigate whether the vaccine protects them.
This is not the first attempt to get a DFTD vaccine off the ground. A 2017 study1 that assessed a vaccine based on modified devil facial tumour cells found that just one in five vaccinated devils mounted a strong enough immune response to prevent the cancer from developing. But the results were encouraging, because they indicated that the devil immune system can become better at recognizing tumour cells, says Flies, who was not involved in the study. “Even though it didn’t work, it was very useful,” he says.
The new vaccine will be delivered by injection and in an oral liquid during the trial. But that won’t be possible on a large scale, so in case the vaccine is approved, Flies and his team have come up with a distribution plan that draws on another vaccine for inspiration. The rabies vaccine is delivered in edible bait to protect wildlife populations across the United States and Europe; Flies says a similar approach would be more practical than injecting the Tasmanian devils left in the wild. “We’re certainly not going to catch all those devils and give them a jab,” he says. The team is designing an artificial-intelligence-driven bait dispenser that will deliver the vaccine to devils but not other wildlife, says Flies.
If the vaccine proves safe and effective, Flies and his team will work on adapting it to target both DFT1 and DFT2 in one hit.
Carolyn Hogg, a conservation biologist at the University of Sydney in Australia, says that even if the vaccine only partially shields the devils from DFTD, it could buy them time to breed more and boost dwindling populations. “It just needs to help them live longer than they currently are,” says Hogg. “If they live longer, they can have more breeding seasons.”