Setback for rabbit control plan

Plans to use a genetically modified myxoma virus to depopulate Australia’s rabbit-ravaged landscapes of the continent’s worst mammalian pest have suffered a setback.

Researchers with the Cooperative Research Centre for Pest Animal Control (CRCPAC) at Gungahlin, in the ACT, have found that the modified virus, developed to sterilise female rabbits by inducing an autoimmune response directed against their eggs, produces only temporarily sterility.

Project leader Dr Peter Kerr said while the initial immune response sterilises the female rabbits , they recover rapidly from the autoimmune attack and regain fertility.

Kerr’s team celebrated two years ago when, after 15 years of research, a modified myxoma virus carrying the gene for the rabbit zona pellucida C (ZPC) protein induced sterility in 80 per cent of female rabbits under laboratory conditions.

ZPC is part of a complex of proteins that form a protective translucent, jelly-like coating around the mature ovum. Sperm have to penetrate the zona pellucida to fertilise the ovum, a process that depends on highly specific interactions between ZP proteins and proteins in the head of the sperm.

Computer modelling and field studies of wild rabbit populations have indicated that the technique, called virally-vectored immunosterilisation (VVIS), needs to permanently sterilise between 70 and 80 per cent of breeding female to reduce rabbits to sub-economic numbers across Australia.

Post mortem analysis of the females involved in the original proof-of-concept experiment revealed extensive, inflammatory damage to their eggs and ovaries.

But because the females were sacrificed, it did not become apparent until the experiment was repeated several months later that the antibody-mediated attack induced only transient sterility -- enough, according to Kerr, to disrupt one breeding.

VVIS works, but apparently, not yet with permanent sterilising effect in rabbits. It works well in mice, which provided the first evidence that it could provide a generic technique for controlling Australia’s plagues of mammalian pests like the rabbit, fox, pig, goat, donkey, camel and even urban rats.

CRC researchers have developed an engineered mouse virus, called mouse cytomegalovirus (MCMV) that produces permanent sterility in 100 per cent female mice. MCMV is a member of the herpesvirus family, and unlike the myxoma virus in rabbits, is transmitted by sexual contact.

Kerr says one reason why MCMV may be a more effective vector in mice is that it is a neurotropic virus, that persists in nerve cells where it cannot be eliminated by the immune response.

The virus appears to act is a natural adjuvant to boost and maintain the immune response, and elicits both antibody-mediated and cytotoxic T-cell responses.

CRC researchers have found that the engineered myxoma virus elicits a strong antibody response uon infecting female rabbits, but no cytotoxic T-cell response.

The antibody response rapidly fades and becomes ineffectual within about six weeks, allowing the females to recover and regain fertility.

“It has always been difficult to get a strong, sustained immune response to a ‘self’ antigen,” Kerr said. “You get an antibody response, but then it passes, as if the animal has been passively immunised with antibodies.”

He said CRC researchers are now working to understand why that happened. As a backup strategy, the CRC is revisiting rabbit haemorrhagic disease virus (RHDV), also known as rabbit calicivirus, which devastated rabbit populations in the semi-arid and arid zones after escaping a contained field trial on South Australia’s Wardang Island, in Spencer Gulf, in 1996.

But for some reason, the RHDV epidemic was largely ineffective in higher-rainfall areas. Kerr says one possibility is that the virus failed because it is being out-competed by another rabbit virus that causes a mild, chronic infection.

The CRC has obtained some research funds to investigate this hypothesis, but Kerr says that, by the middle of next year, further research on viral control of rabbits may be shelved because of lack of industry and Commonwealth funding.

Despite the rabbit's notoriety as a pest, and the enormous environmental damage it causes, the pastoral industry has not adequately funded research. Because rabbits are ubiquitous across the continent, and caused such massive to the environment, as well as the grazing industry and other forms of agriculture, rabbits were "always someone else’s problem”, Kerr said.

With Commonwealth funding agencies like the Australian Research Council focusing on research with potential commercial outcomes, there was little enthusiasm for public-good research that did not have a clearly identifiable industry beneficiary.