A Trinity College research group has helped develop a vaccine against drug-resistant bacteria that can infect hospital patients. Dick Ahlstrom reports
A Dublin-based scientist has developed a working vaccine against a common bacterium that causes dangerous infections in hospital patients. He believes this is the first working vaccine against Staphylococcus aureus, the bug that has become resistant to some of our most powerful antibiotics.
"It is looking promising," says Prof Tim Foster of the microbiology department in Trinity's Moyne Institute of Preventive Medicine. The vaccine has been used successfully in a Phase II medical trial of 500 low birth weight premature babies, reducing both mortality and infection rates, he says. "They are planning a Phase III trial later this year."
The vaccine grew out of research in the early 1990s when Foster and his group discovered a novel protein on the surface of the S aureus cell called the clumping factor. "A patent was filed because we realised the potential significance of this for developing a vaccine," he says. "At the time the research was funded by the Wellcome Trust."
Later funding came from BioResearch Ireland, and more recently the Health Research Board, Science Foundation Ireland, Enterprise Ireland and the EU.
The novel protein meant that they had a target unique to S aureus, a bug that has caused death and illness in hospital patients around the world. These bugs are fellow-travellers with us, living harmlessly in the noses of half the population and also commonly colonising the skin.
Some strains have become strongly resistant to the antibiotics designed to kill bacteria, however.
This means they can often survive frontline antibiotics, constantly challenging the drug companies to find new drugs that can kill these strains, known collectively as MRSA (Methicillin Resistant Staphylococcus aureus).
The current antibiotic of last resort, vancomycin, still works against most MRSAs but the medical journals increasingly carry reports about staph resistance to this antibiotic.
"There are a couple of new antibiotics," says Foster. "Resistance will develop very quickly, so we view vaccination as an alternative."
Foster began a collaboration with a company in Houston, Texas, called Inhibitex, a research-based firm that spun out of Texas A&M University. The company grew rapidly and is now based in Georgia in the US and Foster is on the company's scientific advisory board.
Foster searched for other proteins that might serve as alternative targets for S aureus and another staph bacterium, S epidermidis. "We discovered a lot more of these proteins," he says, "cousins of clumping factor." The team noted sequences in the first protein and looked for related ones in the staph genome, mining it and quickly finding 10 more.
"It is like an insurance policy in case anything goes wrong with the primary target, the clumping factor," Foster says.
Together Foster, Inhibitex and other collaborators have filed patents on six further proteins.
Trials are under way on two vaccines, the one used with neonates and based on the use of purified antibodies recovered from human donors and another trial that has just cleared Phase I and is currently enrolling for Phase II.
This vaccine is based on monoclonal antibodies recovered from engineered organisms.
The trial involving the premature babies was a "proof of principle" for this passive transferred immunity approach.
One in five premature babies weighing less than one kilogram at birth will get staph infections, says Foster, hence the group's interest in a vaccine.
Yet any patient would benefit from a staph vaccine before heading into hospital for surgery or emergency treatments. Patients who have to use catheters and young people may be particularly vulnerable too. "They are all at risk of staph infection," says Foster. "Some 40 to 50 per cent of hospital acquired staph infections are caused by MRSA."
The great advantage is the vaccine delivers antibodies, so treatment can be given to patients who already have infections.