# Chlamydial Vaccine Testing in Mice and Guinea Pigs

> **NIH NIH U19** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $533,605

## Abstract

Chlamydia trachomatis (CT) is the leading cause of tubal obstruction and infertility in the US and
globally. Similar to humans, primary chlamydial infection in rodent models induces immunity that is
partially protective against subsequent challenge. IFN-producing CD4 T cells (Th1 cells) are
essential for resolving infection and resisting reinfection. CD8 T cells can contribute to resolution
through production of IFN, and antibodies augment resistance. Studies in mice and guinea pigs
demonstrated that the induction of Th1 cells in the FGT by infection or vaccination correlate with
protection. Tissue resident memory IFN-secreting CD4 T cells (Th1 TRM) were shown to be critical
for long-term immunity in mice. These findings support our hypothesis that an efficacious chlamydial
vaccine will therefore need to induce both systemic Th1 and FGT Th1 TRM. Animal models are
essential for iterative testing of vaccines to provide essential immunogenicity, mechanistic, and
efficacy data for progressing vaccines to the clinic. We have standardized mouse and guinea pig
genital tract challenge models for testing chlamydial vaccines. We will examine two leading T cell
vaccine modalities proven safe in humans for the development of novel chlamydial vaccines. The first
is a heterologous virus vector prime boost regimen comprised of a chimpanzee adenovirus (ChAd)
prime followed by a Modified vaccinia virus Ankara (MVA) boost shown to induce high frequencies of
CD4 and CD8 T cells. We will generate and test the first ChAd/MVA vaccines against chlamydia. The
second platform uses a proprietary nanoemulsion Nanovax to adjuvant recombinant proteins.
Nanovax vaccines are specifically formulated for intranasal delivery and efficiently induce mucosal
CD4 T cells and antibodies. We will develop and test trivalent Nanovax vaccines against
Chlamydia. The immunogens used will be species-specific homologs of CT proteins that have
documented immunogenicity in women who resisted reinfection or limited the extent of their CT
infection. We will use these vaccine modalities to pursue three specific aims: Aim 1. Evaluate the
immunogenicity and protective efficacy of replication-deficient viral vectors expressing chlamydial
antigens in mice. Aim 2. Evaluate the immunogenicity and protective efficacy of recombinant
chlamydial antigens delivered intranasally via NE in mice and the ability of combined vaccines to
improve protection. Aim 3. Determine the immunogenicity of ChAd/MVA prime-boost and NE-
adjuvanted chlamydial vaccines in female guinea pigs and their ability to protect from artificial and
sexual transmission of C. caviae alone and in combination. This project will identify novel chlamydial
vaccines with a highly feasible path to clinical testing and licensure.

## Key facts

- **NIH application ID:** 10149923
- **Project number:** 5U19AI144181-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Nilu Goonetilleke
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $533,605
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149923

## Citation

> US National Institutes of Health, RePORTER application 10149923, Chlamydial Vaccine Testing in Mice and Guinea Pigs (5U19AI144181-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10149923. Licensed CC0.

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