# Novel antigen designs and delivery platforms to enhance the protective ability of Tpr-based vaccines for syphilis

> **NIH NIH U19** · UNIVERSITY OF WASHINGTON · 2021 · $466,872

## Abstract

ABSTRACT
Over the last two decades, our efforts to develop a syphilis vaccine have allowed identification of two
antigens that confer high but not complete protection to syphilis in immunization/challenge experiments in
the rabbit model. These two vaccine candidates were derived from conserved regions of selected members
of the Treponema pallidum repeat (Tpr) antigens TprC/D2 and TprK. Immunity to these antigens has been
shown to enhance pathogen clearance by opsonophagocytosis and provide substantial protection from
chancre development at challenge sites compared to controls. In these early vaccine designs, however,
several predicted surface epitopes of the TprC and TprD2 proteins were omitted because they showed a
limited degree of antigenic variation, even though we demonstrated that they could provide additional
targets for pathogen opsonization and phagocytosis by activated macrophages if used in combination with
adjuvants inducing a Th1-type response.
To attain a fully protective syphilis vaccine we aim to modify our early vaccine design to include additional
protective epitopes of the TprC and TprD2 proteins. First (Aim 1), we will evaluate the protective activity of
full-length recombinant TprC and TprD2 using a cocktail of antigens designed to cover all antigenic variants
of these proteins, which will also contain the TprK conserved fragment. In parallel, we will conduct a series
of experiments to map T-cell epitopes and protective B-cell epitopes of TprC and TprD2 to inform
development of alternative platforms for antigen delivery, with the goal of delivering selected epitopes rather
than on full length antigens. For these mapping experiments (also planned in Aim 1), we will use TprK as a
control antigen, as B-and T-cell epitopes were already identified for this protein in the past. In lieu of
recombinant proteins, we will engineer and test chimeric concatemers (Aim 2) and chimeric HPV-based
viral-like particles (VLPs, Aim 3). These alternative delivery platforms will specifically induce immunity to
targets of opsonizing antibodies on the treponemal surface, and likely enhance pathogen clearance upon
infectious challenge. In Aim 4, we will combine our results and those obtained by Dr. Cameron (Project 1)
with her selected vaccine candidate (Tp0751) to combine our most protective vaccine designs and delivery
platform. Subsequently, a final immunization/challenge experiment with our fila vaccine design will be
performed to assess overall level of protection and durability of immunity using a modern syphilis isolate to
challenge immunized animals following rabbit immunization.

## Key facts

- **NIH application ID:** 10219124
- **Project number:** 5U19AI144133-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Lorenzo Giacani
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,872
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219124

## Citation

> US National Institutes of Health, RePORTER application 10219124, Novel antigen designs and delivery platforms to enhance the protective ability of Tpr-based vaccines for syphilis (5U19AI144133-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10219124. Licensed CC0.

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