# Global sequence and surface antigenic diversity of Treponema pallidum outer membrane proteins

> **NIH NIH U19** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2022 · $625,323

## Abstract

PROJECT SUMMARY ABSTRACT
Syphilis, a multi-stage sexually transmitted disease caused by the spirochete Treponema pallidum (TPA),
continues to be a major worldwide public health problem. Despite the wide availability of antibody (Ab)-
based screening tests and effective antimicrobial therapy, syphilis control strategies have met many
challenges, particularly in resource-poor countries where proper diagnosis and partner services to reduce
transmission are not always feasible. The inability of traditional public health prevention strategies to
curtail the spread of venereal syphilis underscores the critical need to develop a safe and effective vaccine
that has global coverage. The current proposal (U19- CRC Project 2) embodies a novel translational
approach that will greatly contribute towards syphilis vaccine development that builds upon our extensive
understanding of the basic membrane and molecular biology of the syphilis spirochete (U19 CRC Project
1) and reverse vaccinology methods that can interrogate the antibody (Ab) responses the bacterium elicits
in its human host to distinct and unique TPA outer membrane (OMP) targets. It is our contention that
the characterization of TPA OMP antigenic targets and their variants, on a global scale, will lead us to
syphilis vaccinogens whose ability to induce opsonic antibodies and protection can be tested (Aims 1, 2
and 3). Two major developments stemming from our microbiologic, immunologic and translational
studies position us to test our unifying hypothesis. First, we have made significant progress
characterizing TPA's repertoire of rare OMPs (U19 CRC Project 1) and second, we have made refined
existing and developed new methods to assess the presence of opsonic anti-OMP antibodies in patient
sera and how antigenic diversity in these targets affects their ability to recognize circulating TPA (Project
2 and 3). Collectively, our syphilis clinical network in the United States, Colombia, Malawi and China,
steered by an expert group of physician scientists, epidemiologists, immunologists and microbiologists,
genomics and analytics experts, lay the necessary groundwork to enroll and study early syphilis patients
at a global scale (Aim 1), collect and extract TPA DNA to understand the complete assortment of OMPs
that are expressed globally by circulating TPA (Aim 2), and understand if syphilitic Abs are indeed able
to recognize candidate vaccine antigens and their antigenic variants (Aim 3). In the end, our approach
will lend itself to formulate and test candidate TPA OMP antigens and model the effects of such a vaccine
that can be used globally.

## Key facts

- **NIH application ID:** 10399447
- **Project number:** 5U19AI144177-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Juan C Salazar
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $625,323
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399447

## Citation

> US National Institutes of Health, RePORTER application 10399447, Global sequence and surface antigenic diversity of Treponema pallidum outer membrane proteins (5U19AI144177-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10399447. Licensed CC0.

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