# Biological Vulnerability to Chlamydia trachomatis in Adolescents and Young Women: the Complex Intersection of Cervicovaginal Microbiome, Cervical Maturation, and Mucosal Immunity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $680,407

## Abstract

Abstract
Females aged 15-24 years consistently have the highest rates of Chlamydia trachomatis (CT) that is implicated
in 40-50% of salpingitis, a primary cause of infertility. Biologic vulnerability to CT is often attributed to cervical
epithelial immaturity, but is likely much more complex and lies in the relationships among cervical topography,
immunity, and the cervicovaginal microbiome (CVM) and its functional state. Data suggest that CVMs
dominated by anaerobes and L. iners are linked to increased CT risk, whereas L. crispatus-dominant CVMs
appear protective. Once infected, immune responses are diverse, ranging from minimal response to over-
active response with the risk of tissue damage and sequelae. Pre-existing inflammation may predispose to
over-active responses. In vivo studies of biologic vulnerability have been difficult since prospective data is rare.
We have the unique opportunity to utilize a biorepository from the HPV Natural History Cohort (R37CA51323;
PI Moscicki), a 25 year prospective study of 1500 women aged 13-24 years at entry, which has over 10 million
datapoints and 200,000 stored biologic samples collected at 4-6 month intervals. CT testing was routinely
performed annually and anytime the patient had symptoms. Our Aims are to examine: 1) associations
between the CVM and its functional state, and risk for CT acquisition, 2) whether the CVM and cervical
maturation status are synergistic in influencing the risk for CT; 3) whether the CVM and its functional state prior
to infection predicts the level of inflammatory response during infection. We hypothesize that L. crispatus-
dominant CVMs lower the risk of CT acquisition via metabolomic profiles that include higher levels of organic
acids, glucose consumption, and little inflammation. CVMs dominated by diverse anaerobes or L. iners raise
the risk with lower levels of organic acids and higher levels of inflammation. Larger areas of cervical immaturity
are more likely to harbor harmful CVMs. Pro-inflammatory states found pre-infection will be associated with
destructive inflammatory responses during infection, leading to loss of epithelial integrity. Aims 1 & 2 will use a
nested case-control design (100 cases, 200 controls), where selected visits reflect 3 time points per woman (2
CT(-) and 1 CT(+) visits for incident cases, 3 CT(-) visits for controls). Biologic factors measured at the CT(-)
visits for cases will be compared to those for controls who represent a similar at-risk population. Aim 3 will
focus on the 100 cases. Biologic measures at the pre-CT visit will be tested as predictors of the immune
response to incident CT. Data will include: colpophotos for cervical maturity; cervical saline washes for CVMs,
metabolomics, cytokines, proteomics; and detailed interviews for patient history. Data analyses will examine
this highly multivariate longitudinal data. Statistical and bioinformatic approaches will include a combination of
mixed effects longitudinal models, weight...

## Key facts

- **NIH application ID:** 9987507
- **Project number:** 5R01AI137680-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Loris Y. Hwang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $680,407
- **Award type:** 5
- **Project period:** 2018-09-13 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987507

## Citation

> US National Institutes of Health, RePORTER application 9987507, Biological Vulnerability to Chlamydia trachomatis in Adolescents and Young Women: the Complex Intersection of Cervicovaginal Microbiome, Cervical Maturation, and Mucosal Immunity (5R01AI137680-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987507. Licensed CC0.

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