Global cases of syphilis are on the rise, prompting public health officials to seek effective strategies to halt its spread. Recent research, conducted collaboratively across four continents, has identified potential targets for a vaccine against this sexually transmitted infection.
Syphilis is a sexually transmitted disease that emerged in Europe around 500 years ago. Its early symptoms can vary significantly, but the bacterium responsible for syphilis can remain in the body for years, often targeting the central nervous system, and can lead to birth defects if transmitted to infants in utero. The availability of injectable penicillin in the mid-20th century led to a decline in syphilis cases, and by the 1990s, the infection became relatively rare due to shifts in sexual behavior after the HIV epidemic.
However, syphilis has recently resurged, with the Centers for Disease Control (CDC) reporting 207,255 cases in the U.S. in 2022—the highest number since the 1950s—of which 3,755 were in newborns, including some stillborns. Other nations are also experiencing similar worrying trends.
Combating the spread of syphilis has emerged as an urgent public health priority. An international team of researchers and medical professionals has compiled one of the most comprehensive genomic studies of the syphilis bacterium to date, correlating genetic data with the clinical profiles of the individuals whose samples were used. They are looking for consistent proteins on the surface of the bacterium, which could serve as potential vaccine targets. Their findings were published in the September edition of Lancet Microbe.
Past scientific investigations using whole genome sequencing of the syphilis-causing bacterium, Treponema pallidum subspecies pallidum (commonly referred to as TPA), have advanced our understanding of the different strains present worldwide. Nonetheless, limited analysis has been done regarding TPA clinical and genetic diversity to guide syphilis vaccine development.
This study involved participants from four countries: Colombia, China, Malawi, and the U.S. The inclusion of TPA genome samples from Africa and South America, which had been previously underrepresented, significantly enriched the TPA genetic database.
After gathering the samples, they were sent to the University of North Carolina’s Institute for Global Health and Infectious Diseases in Chapel Hill (UNC-Chapel Hill) for genetic mapping in Dr. Jonathan Parr’s lab.
“Whole-genome sequencing of samples collected globally has enhanced our understanding of circulating Treponema pallidum strains. These results are vital for recognizing differences between strains and identifying targets for vaccine development,” stated Parr.
The researchers’ genetic analysis and protein modeling revealed significant differences in syphilis bacteria across continents, yet also highlighted enough commonalities to believe that viable targets for a universal vaccine could be identified.
Professor Justin Radolf from UConn School of Medicine, a senior author on the publication and a Principal Investigator of the NIH U19 award supporting the research, underscored the significance of these discoveries.
“By mapping genetic mutations to three-dimensional models of the bacterium’s proteins, we’ve gained vital insights that will guide the design of a syphilis vaccine,” Radolf explained.
Researchers at UNC-Chapel Hill are evaluating vaccine acceptability to understand potential concerns regarding participation in future trials and the prospective impact of a syphilis vaccine on at-risk populations.
“Engaging with the community is crucial to gauge patient perspectives and reservations about an upcoming syphilis vaccine trial, even before the vaccine is developed,” commented Dr. Arlene C. Seña from UNC-Chapel Hill, co-lead of the global clinical study and lead author of the Lancet Microbe paper.
The research team has already obtained funding to continue their efforts in developing a syphilis vaccine.
“This study showcases the effectiveness of collaboration,” said Juan Salazar, Physician-in-Chief at Connecticut Children’s and co-lead of the project, who also chairs the pediatric department at UConn School of Medicine. “Our endeavor addresses not only a local health issue but also contributes to a global resolution for a disease affecting millions worldwide.”
This research received support from grants provided by the National Institutes of Health (NIH), the Bill & Melinda Gates Foundation, Connecticut Children’s Medical Center, and several international research institutions.
