# Host Immune Responses to Chlamydia trachomatis Candidate Vaccine Antigens and their Association with Clinical Correlates of Protective Immunity in Women

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $672,738

## Abstract

Prevention of Chlamydia trachomatis (CT) infection is a public health priority because it causes reproductive
sequelae. Since CT control programs have not reduced infection rates, a CT vaccine is needed. Our long-term
goal is to generate knowledge that will advance CT vaccine development. One obstacle to CT vaccine
development had been identifying immune and clinical correlates of protection in humans. We showed that CT-
specific systemic CD4+ IFN-g is a correlate of immune protection in women and that spontaneous clearance of
CT infection before treatment and absence of reinfection after treatment are clinical correlates of protection. With
sparse data on CT-specific mucosal cellular immune responses in women, we developed a novel approach for
studying these responses using mucosal mononuclear cells (MMCs) from menstrual blood (MB). Another
obstacle in CT vaccine development has been identifying CT antigens that induce protective immunity. Using an
immunoproteomic approach, Dr. Brunham’s laboratory identified five CT outer membrane proteins (OMPs) that
elicited strong T helper type 1 (Th1) responses. They tested a CT and C. muridarum subunit vaccine that
combined these OMPs with a Th1 polarizing adjuvant and found it accelerated infection clearance in mice.
 The potential immunogenicity of these CT OMPs and need for a CT vaccine provides strong rationale for
extending immune studies of these promising CT antigens and others to humans. The major objective of our
proposal (in response to FOA PA-19-096) is to study cellular and antibody responses to promising CT vaccine
candidate antigens. Our hypothesis is that Th1 cytokine responses against candidate CT antigens will be
associated with clinical correlates of protection and may correlate with functional antibody responses against CT
organisms (EBs). Our study has 3 aims: Aim 1 - Investigate systemic cellular and humoral immune responses
to candidate CT vaccine antigens and their association with clinical correlates of protection against CT in women.
Peripheral blood mononuclear cells (PBMCs) from women with spontaneously cleared vs. persisting CT infection
and women without vs. with CT reinfection will be stimulated ex vivo with promising CT vaccine candidate
antigens and CD4+ and CD8+ T cell responses measured by intracellular cytokine staining (ICS). Sera will be
tested for IgG to CT antigens and functional antibody responses to CT EBs. Aim 2 - Evaluate mucosal T cell
and antibody responses induced by candidate CT vaccine antigens and their association with clinical correlates
of protection against CT in women. From Aim 1 participants, MMCs from MB will be stimulated ex vivo with CT
antigens and CD4+ and CD8+ T cell responses measured by ICS. Mucosal antibodies to CT antigens will be
tested. Aim 3 - Use an in vitro human dendritic cell / CD4+ T cell co-culture method (MIMIC system) to confirm
antigenicity and immunogenicity of promising candidate CT vaccine antigens in women. PBMCs from CT naïve...

## Key facts

- **NIH application ID:** 10051002
- **Project number:** 1R01AI148359-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** WILLIAM M GEISLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $672,738
- **Award type:** 1
- **Project period:** 2020-05-11 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051002

## Citation

> US National Institutes of Health, RePORTER application 10051002, Host Immune Responses to Chlamydia trachomatis Candidate Vaccine Antigens and their Association with Clinical Correlates of Protective Immunity in Women (1R01AI148359-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10051002. Licensed CC0.

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