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

The Weekend Australian - Travel - - Health -

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.’’

Pic­ture: David Sproule

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

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