# Syphilis Immunology and Biology to Improve Clinical Management and Vaccine Design

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $706,759

## Abstract

PROJECT ABSTRACT
 The proposed study will help substantially advance understanding of the immunology,
biology, and detection of syphilis, through the study of newly identified cases in Lima, Peru,
where syphilis is hyper-endemic. Syphilis remains a serious disease with significant adverse
clinical outcomes. Despite over 100 years of research in the biology of Treponema pallidum
sub. pallidum, the bacterial pathogen that causes syphilis, the use of modern methods to study
this infection is just beginning, with our team spearheading some of this work. Our study builds
on the research infrastructure and capacity created through two previously NIH-funded studies,
the “Picasso Study” (NIH/NIAID R01AI09972) and “Picasso 2” (NIH/NIAID R01AI139265) as
well as an SBIR grant (R43AI149804). In this proposal, investigators from USC, UPCH, UW,
and Antigen Discovery will work together to accomplish the proposed three aims and fill critical
gaps in the understanding of syphilis.
 Aim 1: Clinical cohort and epidemiology — Hypothesizing that those with a first versus
repeat syphilis infection will demonstrate different immunological profiles, we will conduct a
prospective study of incident syphilis cases, comparing those with and without a history of prior
syphilis infection. We will a) recruit, treat, and follow 50 individuals with incident syphilis without
prior infection and 100 individuals with repeat syphilis infection. We will compare individuals with
de novo versus repeat infection with two outcomes: 1.the proportion with clinical manifestations
of syphilis at diagnosis and 2. rates of re-infection during follow-up. Aim 2: Immunological —
Hypothesizing that the clinical manifestations and immunologic responses (antibody responses
and T cell activation) will differ between individuals with repeat infection versus de novo incident
syphilis infection (active versus treated infection), we will investigate antigens associated with
reinfection, identify TP proteins that activate a CD4 T cell response, and document the T cell
receptor response to infection and treatment. Aim 3: Transcriptomics — we will analyze the
host transcriptome to identify diagnostic signatures for syphilis. Assays for syphilis remain
limited in their ability to differentiate between active and resolved infection. In this study, RNA-
seq data from whole blood collected pre and post treatment will be used to identify transcription
pathways involved in functional immunity to syphilis.
 Building on our years of ongoing collaborative work in syphilis pathogeneses and
diagnostics, this proposal will focus on new areas of syphilis immunology to inform vaccine
discovery and novel diagnostic test development.

## Key facts

- **NIH application ID:** 10801853
- **Project number:** 2R01AI139265-06
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Jeffrey David Klausner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $706,759
- **Award type:** 2
- **Project period:** 2018-09-01 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801853

## Citation

> US National Institutes of Health, RePORTER application 10801853, Syphilis Immunology and Biology to Improve Clinical Management and Vaccine Design (2R01AI139265-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10801853. Licensed CC0.

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