# DYNAMICS OF M. TUBERCULOSIS-SPECIFIC INNATE AND ADAPTIVE IMMUNITY DURING PREGNANCY AND POSTPARTUM IN WOMEN WITH HIV

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2022 · $243,843

## Abstract

Tuberculosis (TB) is the most important cause of morbidity and mortality among people with HIV in low-income
settings. Isoniazid prophylactic therapy (IPT) is currently recommended for people with HIV in areas of high TB
endemicity and in those with evidence of latent TB infection (LTBI+) in nonendemic areas. TB predominantly
affects young adults, including women of reproductive age. Unlike other infections with intracellular pathogens,
which carry highest morbidity during pregnancy and first 2 weeks postpartum, the incidence of active TB
infections (ATBI) does not increase during pregnancy, which is surprising in view of the significant loss of M.
tuberculosis (Mtb)-specific Th1 responses measured by interferon gamma release assays (IGRA) during
pregnancy. The loss of IGRA responses during pregnancy is likely due to the increased frequency of regulatory
T cells (Treg), which probably also account for the increased morbidity of influenza, varicella and malaria
during pregnancy. We hypothesized that Mtb-specific trained immunity and memory responses (Tmem)
are maintained during pregnancy, while Th1 and Th17 effector responses (Teff) decrease and Treg
increase. We will address this hypothesis in AIM 1 using peripheral blood mononuclear (PBMC) archived in
IMPAACT P1078, which randomized pregnant women with HIV to initiate INH antepartum (AP) or postpartum
(PP).
AIM 1. To evaluate the effect of pregnancy on trained immunity, Th1, Th17 and Treg responses to Mtb.
Subaim 1a. To compare trained immunity, Th1, Th17 and Treg responses to Mtb between AP and PP.
 Hypothesis: Th1 and Th17 effector responses to Mtb are lower, Treg are higher, and Tmem and trained
 immunity do not change from AP to PP.
We will use 40-color spectral flow cytometry and RNAseq on samples collected at study entry and at 12 weeks
PP from women who started IPT at 12 weeks PP.
Subaim 1b. To evaluate the relationship of responses to Mtb with pregnancy-induced circulating Treg.
 Hypothesis: Increased frequency of circulating Treg is associated with decreased Teff responses to Mtb
 during pregnancy. Other potential associations will be examined for the first time to generate new
hypotheses.
We will measure the frequency of circulating Treg AP and correlate them with Teff and other responses to Mtb.
AIM 2 will evaluate the effect of IPT on Mtb-specific Th1 and Th17 responses and trained immunity. Th1 Teff
have been shown to decrease after treatment of ATBI or IPT in people without HIV. This is probably due to
decreased antigenic stimulation of Th1 Teff due to elimination of Mtb replication. There is a dearth of
information on the effect of treatment on Mtb-specific immunity in people with HIV. However, this information is
very important due to the increased loss of Mtb-specific T cells in the context of HIV infection. Using PBMC
collected in P1078, we will test the hypothesis that IPT is associated with a decrease in Mtb-specific
Th1 and Th17 cells, but it does not affect trained immunity...

## Key facts

- **NIH application ID:** 10356601
- **Project number:** 1R21AI155257-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** ADRIANA WEINBERG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $243,843
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356601

## Citation

> US National Institutes of Health, RePORTER application 10356601, DYNAMICS OF M. TUBERCULOSIS-SPECIFIC INNATE AND ADAPTIVE IMMUNITY DURING PREGNANCY AND POSTPARTUM IN WOMEN WITH HIV (1R21AI155257-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10356601. Licensed CC0.

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