Syphilis vaccine-A hope ahead

The number of people suffering from syphilis is creeping day by day. Researchers are working since long to eliminate syphilis by treating people who contract it, tracking down the patients' recent sex partners, treating them and their partners, until the healthcare workers found everyone who could have been exposed to the disease but unfortunately this methodology is confined to people's willingness and ability to reveal their sexual contacts and the difficulty faced in diagnosing syphilis.

It is the second leading cause of stillbirth and miscarriage worldwide and, if left untreated, can cause strokes, dementia, and other neurological diseases.

Treponema pallidum, the causative agent of syphilis, cannot be cultivated continuously in vitro. It is among the most poorly understood of all human bacterial pathogens. The relatively small size of the T. pallidum genome accounts for the fact that the spirochete lacks many of the genes encoding biosynthetic pathway.

Besides humans, the only animal commonly found in laboratories that is susceptible to syphilis is the rabbit. However rabbits clear syphilis infections quickly, so new rabbits must be infected regularly to maintain a strain of Treponema pallidum. Further syphilis is hard to study because the bacteria is so delicate that it does not survive under dry conditions or when washed. It tends to break open and spill its guts, making it impossible to figure out which proteins are supposed to be on the outside of the bacteria.

The researchers got a major breakthrough after the genetic analysis became available. Justin Radolf and Melissa Caimano analyzed the genetic code of T. pallidum. They collected samples from patients from different regions and found that the strains from different places were very similar. Not many genes differed and in an organism with such a small genetic code, every gene must be essential. The genes would only mutate into a different form if it was a matter of life and death.

"They're mutating to avoid the immune system," Radolf says. Radolf and Caimano's team suspected that these mutating genes coded for the proteins they were looking for. So they began testing them. They used a computer modeling program to model the proteins these genes would make, and see if those proteins had the characteristic barrel shape that bacteria use for proteins on their outer membranes. It turned out that many of them did.

The researchers then actually made the proteins and tested whether they folded into that barrel shape in real life. And then finally, they made antibodies for the proteins and showed that these antibodies did indeed attach to the exteriors of intact T. pallidum bacteria. This meant that they had found their marks and the proteins were there.

The researchers found that proteins mutated a lot to hide from the immune system and are not good candidates for a vaccine. For a vaccine, the opposite; proteins are needed that are always the same in every syphilis bacteria. So the final work for the researchers was to go back through T. pallidum's genetic code to find genes that coded for proteins in the outer membrane that never changed, using the genes they had already found as clues.

"You want the best candidate outer membrane protein for a vaccine, the one that varies the least," says Caimano.

Finally, the researchers found the genes that coded for proteins in the outer membrane that never changed, and now the researchers plan to use them to immunize rabbits to prove they could work as a vaccine. They are also looking for even more diverse types of syphilis.

The UConn Health researchers will be collaborating with researchers at the University of North Carolina to enroll patients in Guangzhou, China, and Lilongwe, Malawi to make sure syphilis they have been studying is representative of syphilis worldwide. If the vaccine can be developed from the proteins the researchers have identified, then it will really prove beneficial for the worldwide syphilis patients.

The World Health Organization estimates that 10.7 million people between the ages of 15 and 49 had syphilis in 2012, and about 5.6 million people contract it every year and the disease is on the rise due to increasing homosexuality and rise of sex workers.

The article was published in the journal mBio.