Vaccinating wildlife with GM viruses could stop diseases jumping to humans, scientists suggest

Vaccinating wildlife with genetically-modified viruses could help stop future zoonotic diseases such as Ebola jumping from animals to humans, researchers say.

But proving the safety and effectiveness of such an approach will be a challenge, say other scientists.

Viruses ranging from HIV to Hendra, and Ebola to MERS all have their origins in wild animal populations, and scientists have been trying to work out ways to vaccinate these animal hosts before the viruses they carry become established in humans.

One idea is to engineer a piece of the disease-causing organism — be it Ebola or Hendra virus — into a virus that normally infects the animals without causing disease, and to rely on it transmitting through the host population.

In a recent issue of Expert Review of Vaccines, a team from the United Kingdom and Australia called for a focus on such "self-disseminating vaccines" to combat emerging infectious diseases.

"The idea is to interrupt the transmission cycle — to go out into the bush, wherever that might be, and vaccinate the carrier population," said co-author Dr Alec Redwood from Murdoch University's Institute for Immunology and Infectious Diseases.

"You might infect a number of animals in a group and then hope that it the vaccine spreads naturally... and reduces the incidence of transmission to humans."

Recently, Dr Redwood's colleague, Dr Michael Jarvis, from Plymouth University, showed he could protect mice from Ebola by injecting them with a mouse cytomegalovirus (CMV) — a genus of virus in the herpes family — that had been engineered to expressed part of the Ebola virus.

Dr Redwood said a similarly-engineered virus could be injected into wild animals, such as gorillas, to stop the spread of diseases such as Ebola.

Such an approach might also be useful in stopping transmission of Hendra or other diseases from bats, Dr Redwood added.

"Bats live in really large communities, so if you could get the virus into a few of those, then the transmission would probably be quite rapid," he said.

Challenges ahead: effectiveness

While studies suggest this approach can work in principle, to be effective as a vaccine, the virus would need to be able to survive and spread just as well as the wild type, so it can transmit properly.

Thus far, research by Dr Redwood has shown difficulty in getting mouse CMV to transmit between mice in the laboratory.

"The working hypothesis is that mice need the stress of being in the wild for CMV to transmit easily," he said. "I suspect it's because the lab is too clean."

Dr Peter Kerr of the University of Sydney and CSIRO Health and Biosecurity said other challenges include working out how to effectively deliver the vaccine to establish herd immunity.

It will also be important to determine whether booster vaccines are needed, and whether the target species is the only host of the pathogen, he said.

"In the case of Ebola virus we really know very little about its natural history but at least great apes, duikers [a type of African antelope] and bats have been implicated in possible transmission to humans," Dr Kerr said.

"Determining whether the vaccine actually protects the population and prevents transmission to humans is going to be very challenging."

According to Dr Gary Crameri, an emerging infectious disease virologist at CSIRO Australian Animal Health Laboratory, the self-disseminating vaccine approach could be useful in bats.

"With the number of emerging infectious diseases from bats, it may be an option, as the virus could potentially be used to vaccinate against a number of bat borne viruses, said Dr Crameri, who has worked on vaccines against Hendra virus.

Challenges ahead: safety

Dr Redwood said the fact that a self-disseminating vaccine was a genetically-modified organism means it could not be released without "considerable regulatory oversight".

Any engineered virus vector should not be more pathogenic to its host than the wild type, and it must not be more likely to jump to a non-target host, he said.

"It's absolutely critical that it would be species specific."

Some viruses play an important role in the lifecycle of the wildlife reservoir, adds Dr Crameri.

"By changing the virus or making bats immune we may bring about other unforeseen changes to the physiology or immunology of the bat host," he said.

But Dr Crameri said the risks of proceeding needed to be balanced against the risk of the emerging pathogens.

"If we stopped encroaching on the habitats of wildlife driving disparate species together we would lower the risks of emerging infectious diseases," he said.

"But this is unlikely, and so consequently we must look to ever more novel means to manage the increasing risk."

Retired virologist and immunologist Dr Ian Ramshaw, an adjunct professor at the University of Canberra, has direct experience of how modified viruses can surprise scientists.

Dr Ramshaw was part of the CRC for Pest Management Control when it was developing 'immunocontraception' to control rabbit and mouse plagues.

The idea was to inject pests with a disseminating virus that had been modified to trigger an immune response in the animal to its own egg proteins.

While attempting to modify the virus to enhance the production of antibodies in the pest animals, the researchers created a virus that was so powerful it killed all the animals injected, Dr Ramshaw said.

"The mere fact that we created a 'super virus' without having any indications such a thing would occur just shows you what can go wrong. There are unexpected consequences," he said.

"I don't think any genetically-engineered replicating infectious agent should be put into the environment without a clear strategy of being able to recover it from the environment in case things go wrong."

While some things may be picked up in laboratory tests, Dr Ramshaw said viruses may behave in unpredictable ways in the environment.

It may escape quarantine, and it may spread to animals it was not intended for. He points to the example of rabbit calicivirus that was carried by blowflies to mainland Australia, escaping quarantine on Wardang Island.

"It's a bit of dilemma. The chances of something happening might be quite small but if it does happen then you could have a major issue on your hands."