Vaccine development for liver fluke parasite | Innovations

Vaccine development for liver fluke parasite

Vaccine development for liver fluke parasite

Updated 11 July 2013, 11:16 AEST

DESLEY BLANCH : Liver fluke is a worm parasite which infects a large number of animals and humans across every continent. In Australia it is endemic in sheep and cattle pastures in south-east Australia and also affects pigs, goats, alpacas and deer.

Livestock industries are facing serious economic losses as the disease parasite develops resistance to existing drugs.  So the hunt is on to develop a vaccine.

With a time-frame of about five years Professor Terry Spithill and his team will lead a just-funded research project to develop a new vaccine against liver fluke disease and which incorporates data from a breed of sheep in Indonesia which is very resistant to liver fluke.

PROFESSOR TERRY SPITHILL : Liver fluke is what we call a worm parasite. It’s transmitted to animals.  When animals graze on infected pastures they eat a little infective cyst which has been released onto the pastures from infected snails. When the animals eat the cyst the little cyst hatches in the intestine releasing a little parasite about the size of a pinhead. It penetrates through the intestine, goes into the liver and migrates through the liver for about 8 to 10 weeks causing damage, haemorrhage and fibrosis in the liver.

And then as the parasite grows from a little pinhead to about one-and-a-half to two centimetres it penetrates into the bile ducts in the liver, sits in the bile ducts for years and causes chronic problems for animals including blood loss due to the blood sucking activity of the parasite.

It’s a worm parasite that’s transmitted by snails that causes liver damage and it’s the damage to the liver that causes the economic losses, the reduced weight gain, the reduced milk production in dairy cattle, reduced wool production in sheep.

So it’s an insidious parasite in that it tends not to kill animals, it damages animals and causes these hidden effects which show up as major production losses. In very high numbers it can kill sheep and cattle but that doesn’t happen very often.

It’s a parasite that’s found in Australia, right throughout Asia, South East Asia, the Middle East, through Europe and down through Africa.

There are two main species, what we call the temperate liver fluke, which is found in Australia and Europe and the tropical liver fluke which is found in across Asia, South East Asia and Africa and these two flukes are very, very similar. So the work we do on the fluke in Indonesia and a fluke in Australia does inform research on both parasites.

DESLEY BLANCH : And tell us how it affects those subsistence farmers in countries like Indonesia and China and Cambodia?

PROFESSOR TERRY SPITHILL: I’m very experienced with Indonesia. When we were working in Indonesia ten or 15 years ago, a typical subsistence farmer would have four cattle. Those cattle would be used to plough his fields and sow his rice and what have you. The cattle are also like his savings plan, so as the animals grow, when the farmer needs funds for say to fund a wedding or to send his child to university, they’ll sell one animal to generate income. So these animals are both production animals as well as they’re investment for the farmer and his family.

So when the fluke infects these animals, when they come to maturity, the animals will be 15 per cent to 20 per cent smaller; dairy cattle will produce less milk, 15 per cent  to 20 per cent  less milk; it affects fertility so the animals are less fertile so it takes longer for a female animal to become pregnant and the animals which are infected can’t work as well in the field.

DESLEY BLANCH : Now these parasites are developing resistance to drugs. Is this the main reason that you’re developing a vaccine?

PROFESSOR TERRY SPITHILL : That’s probably the primary one. We do have good drugs. The dilemma we have—there is only have one drug which will kill the baby parasite. The important thing about liver fluke is you’ve got to control the parasite early after it enters the liver before it causes too much damage. So that’s what we call the baby or juvenile parasite. And there’s only one drug that kills the baby parasite in the first few weeks of infection and that’s the drug which unfortunately the parasite is developing resistance to in Australia and across the world throughout Europe and Ireland.

And so the problem with drugs, of course, is that it’s inevitable that parasites will develop resistance to drugs. So we think a more sustainable approach is to develop a vaccine. We all know how effective vaccines like small pox and the polio vaccines and measles vaccines are. We believe if we can develop a vaccine, a) it’ll be effective, and b) it’ll be very sustainable and c) it’s probably cheaper for producers to use a vaccine than to be treating animals with drugs three or four times a year.

DESLEY BLANCH : From your research so far, do you think one vaccine will work for different species; you’ve mentioned sheep, and there are cattle and there are goats and then there are humans?

PROFESSOR TERRY SPITHILL : Look, it’s a very good question. I think the short answer is probably; probably with the right molecules. What we find in reality is often vaccines will work better in one species than another and that’s because the immune system of the sheep and the immune system of cattle and humans and goats are not all identical and some animals, for example, this breed of sheep in Indonesia that we looked at have a very strong natural immunity which has evolved--these sheep in Indonesia have evolved with the parasite and have developed this very strong natural immunity which is the immunity we’re using now to try and identify the vaccines.

So I think the short answer is that it’s possible that a vaccine that we develop for cattle work in sheep and other animals. It’s also possible that we may need to tweak the vaccine and the formulation for sheep, for example might be slightly different to the formulation of cattle.

DESLEY BLANCH : So you’re taking that research that’s come from the Indonesian sheep and looking at it alongside the Australian parasite?

PROFESSOR TERRY SPITHILL : Exactly. It’s a very interesting story. Back in the 1990s, the Indonesian government came to the Australian government and said look, we had this problem with liver fluke in livestock. It’s a major constraint for us. Can you help us work on a vaccine to control the disease?

And so ACIAR, in Canberra, the Australian Centre for International Agricultural Research, they funded us for about ten years to do some work on Indonesia on both vaccines and on these sheep. And what we found in these sheep was when we looked at these sheep; we found that they had a very strong natural, what we call a natural immunity. In other words, when the parasite invades these sheep and the little baby parasite gets into the liver, the animal mounts an immune response which is very effective at killing the parasite within a few weeks of invasion and thereby stopping the major damage caused by the parasite.

So what we did is we looked at the immune mechanism in these sheep and to cut a long story short, we found that the mechanism involved the sheep making antibodies which bound to the surface of the parasite, what’s called the tegument and then special white cells in the blood--there are special types of white cells called macrophages oesinophils--they bound to the antibodies, bound to the surface of the parasite and killed the parasite.

So we, for the first time, this is actually the first time anyone had reported an immune mechanism that could kill liver flukes. And so what we’re doing now is we’ve got the hypothesis of that mechanism that exists in sheep in Indonesia.

A similar mechanism will occur; it will be operating in sheep and cattle against the Australian fluke and so we’re now we’re trying to actually identify obviously what are the proteins on the surface of these parasites that’s recognised by the antibodies and can we engineer a vaccine using those proteins.

DESLEY BLANCH : Well, you’ve got Virbac Animal Health Australia on board with you and they’re specialist manufacturers of animal healthcare products. So what cutting edge technologies are available to you to speed up the vaccine development process?

PROFESSOR TERRY SPITHILL : Two things with what’s become available in the last few years. There’s firstly we have what’s called the genetic data bases on the parasite. If you go back ten or 15 years, we didn’t have the genetic information of what were the genes in these parasites and what proteins were coded by those genes. Now have information.

Secondly, we now have information which says which genes are expressed in the baby parasite and which genes are expressed in the adult parasite. And obviously we’re focusing on proteins expressed in the baby parasite, so we had that information.

Thirdly, Virbac as a vaccine company which is now focussed on vaccine manufacture, they have special, what we call, formulations. These are things like adjuvants; these are molecules that we can mix with our, once we get out the protein that we think is a good target, we can mix it with a certain type of adjuvant and a certain type of formulation and that formulation maybe optimal in inducing immune responses in sheep and cattle and goats, for example.

So, by working with a company like Virbac we can harness their experience with vaccine manufacturing, with vaccine formulation. We’re providing the proteins that we think might be the best candidates; Virbac are providing the sort of the vaccine formulation experience and they’re also helping to fund the work, particularly the work in cattle.

We need a vaccine which is effective in sheep and cattle but they’re very expensive experiments to do and they’re very slow experiments, but Virbac have a lot of experience in that area. So it’s a very good collaboration between scientists like ourselves; myself and my students who have the genes and the knowledge about the proteins and Virbac who have the knowledge of how to formulate those proteins to get the best response in animals.

DESLEY BLANCH : Professor Terry Spithill is Co-Director of the new Centre for AgriBiosciences at La Trobe University in Melbourne who says that global losses due to the liver fluke parasite are at least three-billion dollars a year. Coupled with the growing need to feed more people we need more efficient production from the animals which we now have and which can be helped by controlling parasitic diseases.

Contributors

Terry Spithill

Guest

AgriBioscience Professor

Department of Agricultural Sciences, La Trobe University

Co-Director of the Centre for AgriBiosciences, AgriBio, La Trobe University VIC 3086

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