# The Role of the Macrophage in Bacterial Vaginosis Mediated HIV Risk

> **NIH NIH DP1** · UNIVERSITY OF FLORIDA · 2024 · $533,750

## Abstract

Project Summary/Abstract
BV is driver of the HIV epidemic, increasing HIV risk up to 60%. Bacterial Vaginosis (BV) is the most common
vaginal condition among women of reproductive age, with a prevalence of 20-60% globally. Mediated by a non-
optimal vaginal microbiome and characterized by vaginal inflammation, symptoms can cause extreme
discomfort, including burning, vaginal malodor, and vaginal itching. A poorly understood component of BV are
its effects on infiltrating immune cells. Tissue resident macrophages may play a role in increased HIV risk, but
have not been investigated in the context of BV. The objective of this proposal is to determine the effects of a
non-optimal vaginal microbiome on inflammatory macrophage activation and training towards an HIV permissive
phenotype by establishing an ex-vivo macrophage stimulation model. Here we propose to assess changes in
macrophage activation when exposed to vaginal fluid from a global cohort of women (BV and healthy).
Macrophage activation will be characterized using both targeted analyses (HIV associated inflammatory
markers) and multi-level proteomics (epigenetic, total proteome). Vaginal fluid will be characterized using
metagenomics and metabolomics. Computational analyses and machine learning will allow for determination of
the role of unique microbial combinations on macrophage activation. We expect to identify specific microbial
compositions that correlate with an HIV promoting macrophage phenotype. This approach is highly innovative
because it couples machine learning with an ex vivo macrophage stimulation model to study microbiome-
macrophage interactions. Furthermore, vaginal fluid obtained from a global cohort of women in the US, South
Africa, and Ghana will be obtained using a citizen scientist model of recruitment which empowers and educates
participants. BV frequently recurs, and the vaginal microbiome is complexly variable among women. Completion
of the proposed project will advance the field of HIV prevention science, by providing a tool to directly examine
macrophage mediated-HIV risk. Additionally, it will provide a platform to test personalized, microbiome-informed,
probiotic interventions. Further, these finding will be paradigm-shifting as there is no precedent data to determine
if immune cells within the tissue micro-environment can be trained by a non-optimal vaginal microbiome, nor
studies to determine how this impacts HIV risk. Trained immunity has been linked to increased risk of HIV
infection, but has not been previously studied in the context of bacterial vaginosis. Completion of the proposed
study will reveal the effects of the vaginal microbiome on macrophage activation, identifying previously
unassessed novel mechanisms of inflammation. This multi-variate approach allows for deep proteomic and
metabolic characterization of the macrophage, which will provide data to determine the effects of vaginal fluid
on the macrophage training, differentiation and activation. ...

## Key facts

- **NIH application ID:** 10918470
- **Project number:** 1DP1HD115449-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Ivana Parker
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $533,750
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918470

## Citation

> US National Institutes of Health, RePORTER application 10918470, The Role of the Macrophage in Bacterial Vaginosis Mediated HIV Risk (1DP1HD115449-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10918470. Licensed CC0.

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