Researchers are preparing to test a vaccine to curb the spread of a deadly infectious cancer in an iconic Australian marsupial, the Tasmanian devil (Sarcophilus harrisii).
Devil facial tumor disease (DFTD) has killed up to 80% of Tasmanian devils since it first appeared in Tasmania — the large island southeast of mainland Australia — three decades ago, raising fears that the feisty marsupial may disappear.
Devil facial tumor cells spread from animal to animal and infiltrate the devil’s immune system because they produce some of the molecules called major histocompatibility complex class I (MHC-1) proteins, which are used by the immune system to identify malicious invaders. The vaccine targets one of the two forms of the disease and aims to make the tumor cells more visible to the immune system. “This is an exciting step forward,” said 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 similar that technology. The success of the vaccines “gave us the confidence to continue,” Flies said.
Like those COVID-19 vaccines, the DFTD vaccine is delivered to cells by an adenovirus — a virus that normally causes mild cold-like symptoms in humans — that has been genetically modified so that it does not 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 the devil cells, it causes them to produce proteins that exist in tumor cells, but not in most healthy cells. These proteins train the immune system to recognize tumor cells as coming from outside the body. If a tumor invades, the immune system’s memory of the vaccine proteins will encourage the tumor cells to express MHC-1, making it easier for the immune system to see them and mount a attack, says Flies.
The vaccine focuses on devil facial tumor 1 (DFT1), which was first identified in 1996 and has spread across much of Tasmania. Another version of the disease, called devil facial tumor 2, appeared in 2014, and is limited to a small area in the southeast of the island. The cancers spread when devils bite each other during fights over food or mates, and result in debilitating tumors on the face and neck, and inside the mouth.
“These directly transmissible tumors are very rare in nature,” said Hamish McCallum, an infectious disease ecologist at Griffith University on the Gold Coast, Australia. “To have two of the same species is very rare and I don’t think anyone knows what causes it.”
Devil of a job
On June 14, Australia’s Office of the Gene Technology Regulator (OGTR) issued a license allowing Flies and his colleagues to test the DFT1 vaccine in 22 healthy captive Tasmanian devils. Only devils that are free of DFTD and do not have any remnants of the experimental vaccine in their systems will be released into the wild after testing.
“The pieces of the puzzle for making this vaccine fell into place over the past few years,” Flies said. “But we don’t know if it will work until we try.”
The first phase of the trial will test whether the vaccine is safe and elicits an immune response. If that goes to plan, researchers will expose vaccinated and unvaccinated devils to the disease to investigate whether the vaccine protects them.
This is not the first attempt to extract a DFTD vaccine from soil. A 2017 study1 who assessed a vaccine based on modified devil facial tumor cells found that only one in five vaccinated devils mounted a strong immune response to prevent cancer development. But the results are encouraging, because they indicate that the devil’s immune system can be better at recognizing tumor cells, said Flies, who was not involved in the study. “Even if it doesn’t work, it’s very useful,” he said.
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 the event the vaccine is approved, Flies and his team have developed a distribution plan that takes another vaccine for inspiration. Rabies vaccine is delivered in edible bait to protect wildlife populations throughout the United States and Europe; Flies say a similar approach would be more practical than injecting Tasmanian devils left in the wild. “We’re certainly not going to catch all those demons and give them a jab,” he said. The team is designing an artificial-intelligence-driven bait dispenser that will deliver the vaccine to devils but not other wildlife, Flies said.
If the vaccine proves safe and effective, Flies and his team will work on adapting it to target DFT1 and DFT2 in one hit.
Carolyn Hogg, a conservation biologist at the University of Sydney in Australia, said that although the vaccine partially protects devils from DFTD, it could buy them time to breed more and boost the dwindling population. . “It just needs to help them live longer than they currently do,” Hogg said. “If they live longer, they can have more breeding season.”
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