Koalas critical to vaccine trail
Australian researchers hope to steal a march in the global race to develop a vaccine against the country’s fastest-growing sexually transmitted infection. Stephen Pincock reports
ONE sunny Friday morning last month, two medical researchers from the Queensland University of Technology hopped in the car to pay a quick visit to Lone Pine Koala sanctuary, a tourist destination on the outskirts of Brisbane.
But the two scientists, professors Peter Timms and Ken Beagley, weren’t skipping work for a day of sightseeing. Their visit to the koala park was a crucial part of their efforts to develop a vaccine for chlamydia, a disease that is both the most common sexually transmitted infection in humans and a major threat to the future of one of our favourite furry symbols.
Chlamydia is sometimes described as a silent STD epidemic. Although simple to treat with a single dose of antibiotics, many people never seek treatment because they have no symptoms. For a few, this can spell disaster — as in humans as well as koalas, untreated infection can cause infertility.
Over the past decade, reported rates of the disease in this country have more than tripled, and currently stand at around 45,000 new documented cases each year. But these figures are likely to be a dramatic underestimate of the disease’s true incidence.
‘‘ The real number of (new annual) cases could easily be as high as 200,000,’’ says professor Basil Donovan from Sydney’s National Centre in HIV Epidemiology and Clinical Research.
Two years ago, the Commonwealth Government responded to the scale of this growing crisis by committing $12.5 million to raise awareness of the disease, and encourage people to get themselves tested for infection.
Screening programs could help identify infected people who need treatment, says Donovan, but a vaccine is widely considered the best and most cost-effective option for tackling the disease. ‘‘ At the end of the day,’’ he says, ‘‘ we’re never going to be able to control chlamydia without a vaccine.’’
Despite decades of work, however, scientists around the world have yet to succeed in developing an effective vaccine against the bacterium that causes chlamydia, Chlamydia trachomatis .
That lack of success could change, however, if the project Timms and Beagley are currently working on pays dividends. As they reported earlier this year in the journal Vaccine (2007;25:2643-2655), they have found the components of an experimental chlamydia vaccine that have already proven effective at protecting mice from infection.
Untreated chlamydia can have devastating repercussions, particularly for women. In up to 40 per cent of women with untreated chlamydia, the infection leads to a condition known as pelvic inflammatory disease. This in turn can damage the fallopian tubes, which carry eggs from the ovaries to the uterus, sometimes resulting in infertility and potentially fatal ectopic pregnancies.
‘‘ Pelvic inflammatory disease and its resultant complications are a major concern,’’ says Marcus Chen, a doctor at the Melbourne Sexual Health Centre in Carlton. In the US, chlamydia has been deemed responsible for 200,000 cases of infertility each year.
Among men, complications are less common, but they do occur. The US Centers for Disease Control says that the infection sometimes spreads to the epididymis — a tube that carries sperm from the testis — causing pain, fever, and, rarely, sterility.
In the developing world, the same bacterium causes trachoma, an eye disease that can cause the eyelid to turn inwards if left untreated. The eyelashes then rub on the eyeball, resulting in intense pain, scarring and, ultimately, irreversible blindness.
Given all this, it isn’t surprising that the Queensland researchers aren’t alone in trying to develop a chlamydia vaccine.
In February this year, for example, US researcher Ashlesh Murthy reported he had developed an experimental chlamydial vaccine able to prevent infections in mice.
Last year a group of scientists from the Rocky Mountain Laboratories of the National Institute of Allergy and Infectious Diseases said they had a vaccine candidate that seemed promising in test-tube experiments. Drug companies such as Merck, Sanofi-Pasteur and GlaxoSmithKline are also interested.
Where the Australian researchers stand out from this crowd is in the components their vaccine uses to stimulate a protective immune response. Timms, Beagley and their colleagues used sophisticated molecular technology to identify a unique combination of three protein components, or antigens, from chlamydia bacteria.
‘‘ The antigens we’ve come up with are of two sorts,’’ said Timms. Beagley added, ‘‘ The first is from the surface of the organism, which isn’t surprising as those are the parts that our immune system sees most clearly. But equally, we’ve identified intracellular antigens, from inside the organism, which you wouldn’t necessarily predict would be good for a vaccine.’’
So far, the Queensland researchers have only tested these components separately, achieving results that have attracted substantial attention and support from major international pharmaceutical companies.
Their next step is to test the three components together in mice, Beagley says. Those experiments are already under way and should produce results within the next six weeks. From there, the plan is to take their experimental vaccine into guinea pigs.
‘‘ We’re at a stage where, if everything goes according to plan, we’ll be looking for a partner to do human trials in about two years,’’ he says.
Working with koalas is a unique aspect of their work. Chlamydia is rampant among koala populations, causing a kind of conjunctivitis that makes finding food difficult, and infections that render female koalas sterile.
Jon Hanger, the senior vet at the Australian Wildlife Hospital in the small Queensland town of Beerwah, says his team treats some 500 koalas each year for chlamydia. Along with loss of habitat and death by road-kill, he says, the disease is one of the major factors threatening koalas in Queensland and NSW.
Timms and Beagley have been researching chlamydia in koalas for a decade, and made sure that the components of their experimental vaccine for humans also had the potential to protect the animals from infection as well.
Within the next few months they are planning to begin testing of the vaccine in animals at the Lone Pine Sanctuary. During their visit in August, they discussed plans for the study with Jacqui Brumm, the park’s wildlife curator. Having seen more infected koalas than she cares to remember, Brumm is enthusiastic about the project.
‘‘ So many wild koalas suffer terribly from chlamydial infection,’’ she says. ‘‘ We’ve been waiting for a project like this for years.’’
Timms and Beagley hope their work at Lone Pine will directly benefit koalas, but they also think it likely to provide vital information for development of a human vaccine. The researchers will be looking closely at how much protection the vaccine offers koalas as a clue to what level of effectiveness they’re likely to see in human patients.
Unlike most other bacteria, chlamydia lives within human cells, which means the researchers are not expecting to achieve 100 per cent effectiveness.
‘‘ Our aim is to prevent the serious reproductive problems and reduce the infectious burden so you can reduce the spread,’’ says Timms. ‘‘ If we can do that in 50 per cent of the population, it would have major health benefits.’’
In humans, even a vaccine that only protected half of the population would make an enormous difference, says Basil Donovan.
‘‘ It doesn’t have to be extremely effective. A chlamydia vaccine would only have to be around 50 per cent effective and it would drive the prevalence of the disease down,’’ he says.
Marcus Chen knows from experience what a difference this would make. Working in an STD clinic, he has seen first-hand the traumatic impact of people learning they have the disease. ‘‘ They’re often shocked and they’re often anxious, and it’s terrible for their relationships,’’ he says. ‘‘ A vaccine that could prevent chlamydia acquisition could prevent all these problems.’’
Getting close for a cause: Ken Beagley at Lone Pine Koala Santuary, Brisbane. Working with koalas has given Australian researchers an opportunity denied overseas teams