Finally, hope for a syphilis vaccine

June 12, 2018, University of Connecticut
Credit: National Cancer Institute

Despite efforts to eradicate it, syphilis is on the rise. Until now, most health agencies focused on treating infected people and their sex partners but new discoveries may make a vaccine possible, UConn Health researchers report in the 12 June issue of mBio.

The World Health Organization estimates that 10.7 million people between the ages of 15 and 49 had in 2012, and about 5.6 million people contract it every year. In the U.S., its prevalence is growing, particularly among men who have sex with men. In many developing nations, it is growing among women sex workers and their clients.

For a long time, have tried 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 this method is limited by people's willingness and ability to reveal their sexual contacts. It's also limited by the difficulty diagnosing syphilis.

"Syphilis is the great imitator; it can look like hyper pigmentation, or other conditions," says Dr. Juan C. Salazar, chair of pediatrics at UConn Health and physician-in-chief at Connecticut Children's Medical Center.

And, the sexually transmitted disease poses serious consequences. Syphilis is the second leading cause of stillbirth and miscarriage worldwide and, if left untreated, it can cause strokes, dementia, and other neurological disease.

Salazar was born in Colombia, where, in the city of Cali, about seven percent of young, sexually active people have evidence of syphilis.

About 15 years ago, he introduced UConn Health researchers to a group of health care professionals at CIDEIM, an infectious disease research institute in Cali, and they started an ongoing relationship: UConn Health researchers received access to a large population of patients for their studies, and the Cali clinicians and researchers received high-level training in recognizing and treating syphilis.

UConn Health personnel often visit Cali, and researchers from CIDEIM have come to UConn Health to train in advanced laboratory techniques in immunology and molecular biology. It's a good exchange, and it's helped fuel breakthroughs like the one the researchers discuss in their recent mBio paper.

Syphilis is hard to study because, unlike many disease causing bacteria, it cannot be grown in a lab dish or in mice. Besides humans, the only animal commonly found in laboratories that is susceptible to syphilis is the rabbit. But rabbits clear syphilis infections quickly, so new rabbits must be infected regularly to maintain a strain of Treponema pallidum, the syphilis-causing bacteria.

The second reason syphilis is hard to study is because the bacteria causes the disease is so delicate. Most disease causing bacteria are pretty tough—you can wash them, dry them, and then look at their exteriors in great detail under a microscope. T. pallidum doesn't survive that rough treatment. It tends to break open and spill its guts, making a mess, and also making it impossible to figure out which proteins are supposed to be on the outside of the bacteria.

And those proteins on the outside of the bacteria are key—they are how our immune system recognizes bacterial invaders. They are how vaccines work, too. The search to find and identify these proteins in syphilis has taken a long, long time. T. pallidum was first identified in 1905, but until now, no one has been able to figure out which proteins it sports on its .

Researchers have tried all kinds of tricks. When genetic analysis became available, they started looking at T. pallidum's genetic code, in hopes that the genes for its exterior proteins would look like the genes other bacteria have. But T. pallidum is part of the spirochete phylum of bacteria—they're spiral shaped and weird, about as closely related to other bacteria as we are to invertebrates.

Just about the only easy thing about T. pallidum's genetic code is its size: it has only about 1,000 genes, total. That's small. Small enough for a human to analyze.

When UConn Health microbiologists Justin Radolf and Melissa Caimano began analyzing the genetics of the syphilis bacteria they collected from patients in Colombia, as well as the syphilis samples sent to them by collaborators in San Francisco and the Czech Republic, they began to notice that the strains from different places were very similar. Not many genes differed. And that makes sense—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. And what controls life and death for T. pallidum?

"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 they'd found their marks—the proteins were there.

Of course, proteins that mutate a lot to hide from the immune system aren't good candidates for a vaccine. For a vaccine, you want the opposite; proteins that are always the same in every syphilis . So the final step in the team's work was to go back through T. pallidum's to find genes that coded for proteins in the outer membrane that never changed, using the genes they'd already found as clues.

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

They found them, and now the researchers plan to use them to immunize rabbits to prove they could work as a vaccine. They're 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 the syphilis they've been studying is representative of syphilis worldwide. If the proteins they've identified really do end up becoming a vaccine, they want it to benefit as many people as possible.

"Every time you go into a developing country, you need to leave something of benefit to the healthcare providers and their patients," Salazar says. Even better if a vaccine comes out of it that benefits the entire world.

Explore further: CDC: syphilis rates up among U.S. men who have sex with men

Related Stories

CDC: syphilis rates up among U.S. men who have sex with men

April 7, 2017
(HealthDay)—Syphilis rates among men who have sex with men (MSM) have increased significantly in the past two decades, according to research published in the April 7 issue of the U.S. Centers for Disease Control and Prevention's ...

Lymphoplasmacytic infiltrate seen in syphilis, HIV co-infection

June 27, 2016
(HealthDay)—Skin biopsies from patients co-infected with HIV and syphilis have moderate to extensive lymphoplasmacytic infiltrate, according to research published online June 14 in the Journal of Cutaneous Pathology.

Bedside tests for syphilis and yaws tested in sub-Saharan Africa

April 19, 2018
In many countries where the bacterial infections syphilis and yaws are found, there is limited access to diagnostic testing. Now, researchers have tested the use of a point-of-care test for both syphilis and yaws, which allows ...

As newborn syphilis cases rise, maternal screening urged

February 6, 2018
(HealthDay)—Newborn syphilis cases have shot up in the United States in recent years, so an expert panel is reaffirming the need to screen all pregnant women for the infection.

Recommended for you

Marker may help target treatments for Crohn's patients

October 16, 2018
Crohn's disease (CD), a chronic inflammatory condition of the intestinal tract, has emerged as a global disease, with rates steadily increasing over the last 50 years. Experts have long suspected that CD likely represents ...

Polio: Environmental monitoring will be key as world reaches global eradication

October 15, 2018
Robust environmental monitoring should be used as the world approaches global eradication of polio, say University of Michigan researchers who recently studied the epidemiology of the 2013 silent polio outbreak in Rahat, ...

Study traces hospital-acquired bloodstream infections to patients' own bodies

October 15, 2018
The most common source of a bloodstream infection acquired during a hospital stay is not a nurse's or doctor's dirty hands, or another patient's sneeze or visitor's cough, but the patient's own gut, Stanford University School ...

Researchers make essential imaging tests safer for people at risk of acute kidney injury

October 15, 2018
Every year, millions of people undergo medical tests and procedures, such as coronary angiography, which use intravascular contrast dyes. "For the majority of patients, these are safe and necessary procedures. However, about ...

Medical marijuana might help MS patients, but uncertainty remains

October 13, 2018
Medical products derived from marijuana might have a mild benefit in treating symptoms of multiple sclerosis, based on reports from patients.

Do not give decongestants to young children for common cold symptoms, say experts

October 11, 2018
Decongestants should not be given to children under 6—and given with caution in children under 12—as there is no evidence that they alleviate symptoms such as a blocked or runny nose, and their safety is unclear, say ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

SKULLTRAP
not rated yet Jun 12, 2018
The mere existence of STDs proves there is no god.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.