Few organisms lead as ghastly a lifestyle as the blood fluke. It lives in human blood vessels, causes untold suffering and disability in many of the world's poorest countries and kills tens of thousands of people each year.
A research group at Dublin City University may have come up with an answer to this problem, however, in the form of a vaccine designed to kill the fluke soon after it bores into the body. If successful, it could help hundreds of millions of people.
The organism is Schistosoma mansoni, and it causes schistosomiasis, or bilharzia, explains John Dalton, professor of biotechnology at DCU. "It is a parasitic-worm disease that infects more than 250 million people in tropical and subtropical countries," he says. "It kills annually more than 80,000 people."
Dalton leads a research group at DCU that has had considerable success with a vaccine against liver fluke. He is using some of the techniques to develop a vaccine against schistosomiasis, employing genetic technologies and the human immune system to attack the organism from within.
Funded by a Wellcome Trust research grant worth £285,000 (€362,000), the new three-year research initiative involves Dr Sean Doyle of the biology department at NUI Maynooth and Dr Sheila Donnelly of DCU. Enterprise Ireland provided another £68,000 (€86,000) and the Health Research Board's gave £218,000 (€277,000) through its North-South collaboration fund, which links Queen's University Belfast with the research project.
"We hope that in three years' time we will have the information we need to move into vaccine trials in animals and soon afterwards, if they were successful, into human trials," says Dalton.
There are three main species of schistosome, but the work will focus on S mansoni, whose life cycle is particularly gruesome, with humans serving as a key feature of their development and spread.
An aquatic snail starts the growth cycle after infection with S mansoni eggs. These grow into small worm forms called cercariae, then rupture out into fresh water, where they go in search of humans to infect.
Just one-tenth of a millimetre long, the organisms attach themselves to the skin and release powerful enzymes that dissolve the tissues. "These critters have boring devices and detect humans, possibly by a temperature gradient but also by lipids, fats on the skin."
Once through the skin, they migrate into the body, eventually attaching themselves inside blood vessels near the intestines or bladder. They reach sexual maturity in about seven weeks and begin to release hundreds of eggs. The eggs can burrow and are designed to penetrate the intestines or bladder, to be released with urine or faeces into water, where they hatch as miracidia that infect the snails, starting a new cycle of infection.
The adults can survive in the body for more than 20 years, and their eggs cause havoc, inducing blood and fluid loss when they burrow. Many eggs get washed by the blood into the liver, where they cause abnormal growths that harm the function of the organ. Drugs can clear the worms, but people are immediately reinfected - hence the international effort to develop a vaccine.
The adults feed on passing red blood cells, digesting the haemoglobin. The group hopes to exploit this by using a vaccine to raise human antibodies against the worm's essential digestive enzymes. "The follow-on to that is if you could disrupt the digestive process, you could kill the parasite."
The team has identified six target digestive enzymes and the genes that produce them, and will attack these using antibodies. "It is a strategy which our lab has pioneered," says Dalton. "We have in vitro evidence that the antibodies bind to the enzymes and can inactivate them. The questions is, what kind of an immune response do you need to get protection?"
The plan is to transfer the genes into yeasts, so they can be bulked up, purified and then tested as a vaccine. The team will have to mix and match the enzymes to get the most powerful antibody response possible. These antibodies would then block the worm's efforts to feed, killing them off and then keeping them at bay, even if reinfection occurs. The worms would never reach maturity, so egg-laying would cease, breaking the cycle of infection.