Peering through a fringe of eucalyptus leaves, Don the koala greets visitors with an air of unmistakable curiosity. His large and sensitive nose can easily detect the scent of unfamiliar humans, but his tiny eyes seem much less useful. Swollen and half covered by inflamed eyelids, they've been reduced to slits by debilitating conjunctivitis.
Don's perch isn't deep in the Australian bush. It's in an isolation ward at the Australian Wildlife Hospital in the small town of Beerwah, in northeastern Australia. He's one of roughly 500 koalas treated for chlamydia infection each year by the hospital's senior veterinarian, Jon Hanger, and his team.
Infection with Chlamydia pecorum is rampant among Australia's dwindling koala population, for reasons that aren't exactly clear. In addition to the conjunctivitis that can make finding food difficult, the bacterium causes genitourinary infections that render female koalas sterile, Hanger says. Along with loss of habitat and death by road kill, this sexually transmitted infection is one of the major factors threatening the koala in the states of Queensland and New South Wales.
Ninety minutes down the highway from Don's spacious leaf-filled cage, postdoc Chris Barker sits at a bench at the Queensland University of Technology in Brisbane, putting the finishing touches on an experimental chlamydia vaccine that he and his colleagues hope will reduce the burden of the disease in the iconic Australian species.
The vaccine will include three antigens: one from the bacterium's outer membrane, another intracellular protein, and a third that isn't yet characterized. This combination stands out from most human chlamydia vaccine candidates under investigation worldwide, which use only outer-membrane proteins.
Barker and previous PhD student Celia Berry identified this unusual combination by testing an expression library of more than 1,000 C. pecorum antigens in mice. Using computer-predictive modelling, Barker and his principal investigators, microbiologist Peter Timms and immunologist Ken Beagley, have also selected likely T-cell epitopes from among the candidate molecules. "What's mostly important in chlamydia vaccination is T cell-mediated clearance," says Timms. "Antibodies are not enough." Preliminary data in mice show that vaccination boosts clearance of the organisms in the vaginal tract by 50%.
In the next few months, the first field trial of their vaccine candidate gets underway, set to measure safety and immunogenicity. The three antigens will be delivered by injection in combination with one of two commonly used veterinary adjuvants, to some 20 healthy animals. "It's essentially a Phase I clinical trial," says Beagley.
The researchers have modest ambitions. "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% of the population, it would have major health benefits."
"It's not possible to completely eliminate the chance of infection," Beagley adds. "As a rule, all intracellular parasites such as chlamydia and viruses are hidden from the immune system, making them harder for the host to get rid of," Timms says. Ideally, their work in koalas will influence work they're doing to develop a human chlamydia vaccine, he adds.
A short drive from the institute where the scientists work, the Lone Pine Koala Sanctuary will likely be the site of the first trial. Jacqui Brum, the curator of the park, says its tree-shaded enclosures are home to more than 130 koalas, making it the largest koala sanctuary in the world.
"This research project has huge merit because so many wild koalas suffer terribly from chlamydial infection," she says emphatically. "It's quite depressing." At Lone Pine, perhaps half the animals carry the bacterium subclinically, she says, picking up a 4-year-old female called Crumpet, whose deep brown eyes are unaffected by the disease. Brum wants to keep it that way. "See," she says, smiling, "isn't she lovely?"