# Mechanisms and Correlates of Immune Protection against Genital Chlamydia in Humans

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $576,597

## Abstract

Chlamydia trachomatis (CT) infection is highly prevalent and causes significant reproductive morbidity.
Despite prevention and control measures, CT infection rates are at an all-time high and reinfection is common,
suggesting that protective immunity to CT is often insufficient. Control of CT infection will require a vaccine. Our
long-term goal is to determine immunogenetic factors that mediate protection against CT in humans to facilitate
vaccine development. We found that a CT-specific systemic CD4+ IFN-g response was associated with lower CT
reinfection frequency in women. We detected IFN-g in cervicovaginal lavages but could not identify the cellular
source because viable mucosal mononuclear cells (MMC) counts in lavages were too low for functional immune
studies. To solve this, we analyzed menstrual blood (MB) as an MMC source, which yielded sufficient MMC
counts. Preliminary data from MB MMC studies revealed IFN-g-producing tissue-resident memory T cells (Trms)
as an IFN-g source, but other MMC sources of IFN-g have not been studied. Mechanisms by which IFN-g protects
against CT in women remain to be elucidated, but in vitro studies suggest they may include tryptophan depletion,
reactive nitrogen intermediates, glucose starvation, and cytolysis. Our preliminary data suggests that microRNAs
(miRs) and genetic variants also influence CT reinfection risk. We found differential miR expression of select
miRs in relation to CT reinfection. We showed in two distinct cohorts that HLA-DQB1*06 was associated with CT
reinfection risk, however, its role in reinfection has not been established as neighboring HLA variants that may
be in linkage disequilibrium (LD) have not been studied. The goal of this application is to bridge the gap in
knowledge needed for CT vaccine development by determining IFN-g mechanisms and other effector responses
that influence adaptive immunity to CT reinfection and the miRs and gene variants that affect risk for reinfection.
 Our central hypothesis is that protection against CT reinfection is a multifactorial process including IFN-g
produced by CT-specific T cells and other effector responses, which may be regulated by miRs and genetic
variants. Using samples and data from a cohort of women with vs. without CT reinfection, we now aim to further
test this hypothesis through additional research: Aim 1: Evaluate mechanisms through which systemic CD4+ T
cells and MMCs mediate protection against CT reinfection - IFN-g mechanisms and other effector responses
from systemic CD4+ T cells and MMCs will be measured by flow-cytometry-based methods and/or PCR (Subaim
1a) and sera tested for T cell-associated miRs with a miR qPCR array (Subaim 1b); and Aim 2: Determine
whether HLA-DQB1*06 or other neighboring HLA variants in LD strongly predicts CT reinfection risk - DNA will
be sequenced for the HLA-DQ and -DR region and fine-mapping done to identify putative risk HLA variants for
analyses with Aim 1 immune response data. This innovativ...

## Key facts

- **NIH application ID:** 10653095
- **Project number:** 5R01AI093692-09
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** WILLIAM M GEISLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $576,597
- **Award type:** 5
- **Project period:** 2011-12-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10653095

## Citation

> US National Institutes of Health, RePORTER application 10653095, Mechanisms and Correlates of Immune Protection against Genital Chlamydia in Humans (5R01AI093692-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10653095. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*