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Summer 2011 Edition
Published: 24 March 2010
Leaving nothing to fluke - Professor Grace Mulcahy

Parasite vaccines for animal health

If you ever studied biology, you probably have the life cycle of the liver fluke tucked away in some corner of your brain. But while this flatworm may be beloved of science curricula, liver fluke is less welcome in the farming sector, where it is thought to cause global losses of over €1.4 billion each year.

At the moment, liver fluke is controlled by giving livestock drugs to kill the parasites. But a team at UCD has been working on a different approach: to vaccinate the animals by literally teaching the animal’s immune system to recognise a key protein that the fluke uses to live in its host.

It’s a move that stands to reduce the burden of disease as well as the cost of monitoring food products for drug residues. And UCD is leading the charge in a major new European project that aims to come up with a commercial vaccine against liver fluke.

But developing a vaccine against a parasite is not as easy as it sounds, according to Professor Grace Mulcahy, Dean of Veterinary Medicine and Professor of Veterinary Microbiology and Parasitology at UCD.

“Parasites are very complex organisms, it’s not like producing a viral or bacterial vaccine,” she explains. “If a virus is a single Lego brick, the parasite is like the most complicated Lego toy you can make. And these flatworms manage to confuse the immune system of the host - you have to be several steps ahead of them."

Professor Mulcahy has a long-standing collaboration with Professor John Dalton at McGill University in Canada, a UCD graduate whom she met when he was working at Dublin City University in the early 1990s. Together they have been developing a vaccine that homes in on a protein in the parasite called cathepsin. The fluke uses the enzyme to invade tissues of the host animal, for its own nutrition and to try and trick the host’s immune system into ignoring the infection.

Professor Mulcahy and Professor Dalton have shown that if you make a recombinant version of cathepsin in the lab and inject it into cattle, the animals mount an immune response against it. This seems to teach their immune systems to react when they meet the real parasite protein as the fluke infects.

Field trials with this vaccine show it can reduce the parasite burden of an animal by around 50-60 per cent, which could be enough to help control the fluke in livestock, explains Professor Mulcahy. And the new European consortium PARAVAC, which has just kicked off, aims to further develop the vaccine approach.

The project, one of the biggest animal health initiatives ever funded under the European Framework Programme, involves over 20 partners from countries within the EU and from regions where both livestock and trade links with Europe are important: South America, North Africa, Canada and Australia. Led by the Moredun Research Institute in Edinburgh, the €9-million project is looking at both roundworm and flatworm parasites, such as fluke. UCD’s role is to lead the flatworm arm of the project, and Professor Mulcahy will be working with UCD colleagues including Dr Theo de Waal and Dr. Clare Hamilton.

During the four-year study they want to flesh out some interesting aspects, such as the long-term effects of the vaccines on the parasite load, and also whether being infected with liver fluke could be holding the door open for other diseases in cattle.
“Because liver fluke is so good at subverting the immune system of the host, it can potentially interfere with the ability of the animal to deal with other diseases, like bacterial infections,” says Professor Mulcahy. “That aspect will also be included in the project.”

In particular the UCD group wants to explore some of their preliminary findings that suggest if an animal has tuberculosis, a liver fluke infection may make it harder to detect.

“We have done a limited amount of experimental work that shows that could be the case but that’s an artificial situation,” says Professor Mulcahy. “We would really like to see whether that is of significance at field level in large-scale studies.”

The ultimate goal of the European project though is to translate the science into a commercial product that livestock producers can use, and to that end the researchers will be tweaking their candidate vaccines to try and make them more effective, notes Professor Mulcahy.

Having a product in hand or ready to go onto the market at the end of a four-year project is an ambitious target, but she notes that the researchers are hitting the ground running as they have already been working out the science - this is not being done from scratch.

Industry partners in PARAVAC, which include Pfizer Animal Health and Triveritas should also be able to offer insights into how to go from lab to market, she notes.

More generally, Professor Mulcahy hopes the European project will also help to raise the public profile of vaccines and how they can improve animal health.

“I think vaccination has unfortunately got rather a bad press in recent years,” she says. “Vaccines have done more than almost anything else to combat infectious diseases, in both humans and animals in the world and I think it’s up to us to explain to the public how they work. I hope through this project that is one of the things, apart from the scientific work, that we will be able to do.”

Anti-fluke vaccines - easier for consumers to swallow?

Controlling diseases in livestock can be a tricky balance - it's important that medication residues don't end up on dinner plates, and Professor Grace Mulcahy believes that vaccines could offer a useful route to protect cattle from liver fluke infection without contaminating meat or milk.

"At the moment liver fluke and many other parasitic diseases are controlled by giving drugs to cattle to kill the parasites," she explains.

"Because they are drugs, they do persist for a certain amount of time within tissues and farmers have to observe very strict withdrawal periods so that the levels of drugs in meat or milk would be below the levels that are set by the regulatory authorities."

Monitoring this withdrawal is a costly process, and obeying the rules can pose particular challenges in dairy cattle, notes Professor Mulcahy.

"If you are producing beef there is only one point in time, when the animal is killed, that you have to make sure no residues are present," she says. "But in dairy production the cattle are constantly producing milk. So this method of control for dairy production in particular - which is an area that is going to be really emphasised in Ireland in the future - is really very difficult."

But a vaccine approach could help overcome the residue issue, explains Professor Mulcahy, who is involved in a major European project to develop a vaccine against liver fluke.

“With a vaccine you administer it once or at most on two occasions, probably by injection and the persistence would be short. The vaccine would be gone within a week or two. Those residue issues simply don’t exist at all.”

 

Grace Mulcahy in conversation with freelance journalist Claire O’Connell (BSc 1992, PhD 1998).
Produced by UCD University Relations