Syphilis vaccine development remains a high priority with a rising number of congenital syphilis cases worldwide. Unfortunately, vaccine development is still in a pre-clinical phase, and ongoing translational work is needed to identify vaccine candidates targeting highly conserved surface-exposed antigens expressed by geographically diverse strains of Treponema pallidum (TPA). But most TPA genomic sequences originated from strains circulating in high-income countries, and only a small number of low- and middle-income countries (LMIC) are represented in global TPA genomic data.
Arlene C. Seña, MD, MPH, and Jonathan Parr, MD, MPH, researchers with the UNC Institute for Global Health and Infectious Diseases, have received a $1.6M grant from the Bill & Melinda Gates Foundation to lead a new project that will expand TPA genomic data, bridging a critical knowledge gap needed to inform syphilis vaccine development.
The project builds on previous studies of patients with early syphilis infections at geographically diverse locations, involving UNC Project-Malawi and UNC Project-China, supported by the team’s global NIAID U19 consortium, as well as a recently completed project with the University of Washington supported by the Gates Foundation. Dr. Seña says ongoing analysis of 288 new genomes generated as part of the prior foundation study confirms distinct TPA subpopulations, including mutations in genes encoding candidate vaccine targets.
“Another important aspect of our study is the identification of sexually transmitted infections that causes genital ulcer diseases. We found a 23% prevalence of chancroid among study participants previously enrolled at our UNC Project Malawi with genital ulcer disease, which is surprisingly high since chancroid is now considered to be a rare infection globally.”
Designing the Study
To inform vaccine design, the team will increase sampling of individuals in LMICs, with primary and secondary syphilis for TPA molecular detection. Researchers also want to determine the epidemiology of other STIs among participants with genital ulcer disease and suspected syphilis in LMICs, using molecular detection methods.
“This is a great opportunity to bridge knowledge gaps in parts of the world where little to no T. pallidum sequencing has been done to-date,” Parr said. “We will use whole-genome sequencing and other molecular methods to study T. pallidum strains and other causes of genital ulcer disease. We hope that our findings will help improve our understanding of the epidemiology of these infections in our international sites and ultimately lay the groundwork for improved prevention and treatment efforts.”
The study team plans to leverage ongoing collaborations with LMIC sites in the Democratic Republic of the Congo (DRC), Liberia and Peru, where the Institute for Global Health and Infectious Diseases has been working with partners for many years, and build new collaborations in Brazil, and India, to further define TPA genomic diversity among persons with early syphilis.
Each clinical site will undergo training for specimen and data collection following master protocol and standard operating procedures. Studies will recruit people 18 years of age or older, who present for care with one or more ulcerative lesions, rash, or mucous patches, with suspected primary and secondary syphilis.
UNC co-investigators include Peyton Thompson, MD; Natalie Bowman, MD; David Wohl, MD; Farhang Akhakhanian, PhD; and Jane Chen, PhD. Others investigators include Kelly Hawley, PhD (Connecticut Children’s Medical Center); Sam Mampunza, MD, PhD, and Ernest Sumaili, MD, PhD (Congo Protestant University); Adele Benzaken, MD, and Fernanda Fernandes Fonseca, MD, MSc AIDS HealthCare Foundation-Brazil); and Amrose Pradeep, MD, Aylur K. Srikrishnan, MD (YRGCare-India).