# Coordinated studies in monkeys and humans to assess the immunological impact of rectal Chlamydia trachomatis infection on protection against genital infection

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $1,127,093

## Abstract

Project Summary/Abstract
The overarching goal of this proposal is to advance the understanding of the immune response to and
protective effects of rectal Chlamydia trachomatis (CT) infections. CT is the most common bacterial sexually
transmitted disease in the world and is associated with substantial reproductive tract morbidity. Rectal CT is
increasingly recognized as a common infection among STI clinic patients, yet despite its high prevalence, there
is no clear data describing how rectal infection affects the immune response to CT or the risk of reinfection. A
better understanding of how the immune system responds to CT infection is urgently needed to inform effective
chlamydia vaccine strategies.
Animal studies in mice and nonhuman primates (NHP) have demonstrated rectal CT infections as non-
pathogenic and persistent, similar to humans infected with non-lymphogranuloma venereum (LGV) serovars in
the rectum. Furthermore, studies in the murine model have shown that rectal infection confers trans-mucosal
protection against urogenital challenge, suggesting that rectal CT infection causes enhanced systemic and
transmucosal immune responses to CT. It is possible the gastrointestinal tract (GIT) will be an optimal site for
attenuated mucosal CT vaccines. However, more data on immune responses and potentially protective effects
of rectal infection in NHPs and humans are urgently needed and will be provided in the proposed studies.
Mouse and human studies provide evidence that secretion of IFN-γ by CD4+ T cells is essential for any
protective immunity. The role for antibodies is less clear but appears to rely not on direct neutralization of
bacteria, but rather on secondary functions of the Fc region of antibodies in activating innate and effector cells.
Except for a few mouse model studies, the Fc-dependent functions of anti-CT antibodies remain largely
unexplored. This project will provide informative data describing functional CT protective immunity in NHP
(controlled exposures) and human (cross-sectional sampling) studies.
We will conduct complementary studies in the pig-tailed macaque model and in clinical studies to address the
hypothesis that rectal CT infection induces robust anti-CT immune responses that may protect from genital
disease. We will directly test whether rectal infection in macaques protects against subsequent genital
infection. In both macaques and humans, we will define anti-CT immune responses that may correlate with
protection from reinfection and disease: secretion of IFN-γ by CD4+ T cells, presence of anti-CT antibodies in
the mucosa, and functional antibody responses, using new methods to test for Fc-receptor-mediated functions
of anti-CT antibodies. This project is the first step to demonstrate that rectal infection modifies anti-CT
immunity in NHPs and humans, and will provide important evidence as to whether the GIT could serve as a
mucosal delivery site for future vaccination strategies.

## Key facts

- **NIH application ID:** 10818394
- **Project number:** 5R01AI175153-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** DOROTHY L PATTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,127,093
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818394

## Citation

> US National Institutes of Health, RePORTER application 10818394, Coordinated studies in monkeys and humans to assess the immunological impact of rectal Chlamydia trachomatis infection on protection against genital infection (5R01AI175153-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10818394. Licensed CC0.

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