# Immune correlates of LTBI in HIV-exposed infants

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $615,772

## Abstract

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 2 billion of the world's population has latent Mycobacterium tuberculosis (Mtb) infection (LTBI) of
approximately 10% progress to active TB disease. TB disease is a major cause of infant mortality,
to 240,000 childhood deaths in 2015. The risk of death from TB is 3 times higher in children <5 yrs.
age compared to older children. Although much effort is being exercised to develop an effective TB
BCG is still the only approved TB vaccine. Despite BCG vaccination, infants have a high risk of
new TB infections (TBI) and for progression of LTBI to active TB disease. Literature on immunity
in HIV exposed uninfected infants is inconclusive. role of a Th2 bias and
of regulatory T cells (T regs) also need consideration. For this proposal, we have access to
and plasma of maternal-infant samples from a completed IMPAACT trial (P1078). This study was
to test the safety of Isoniazid preventative therapy (IPT) during pregnancy or post-partum in
women who were followed until I year post-partum. Incidence of LTBI was tested by IGRA
gamma release assay). Approximately 30% of the women were IGRA positive at study entry.
infants, approximately 5.6% were IGRA + at 12 weeks and remained positive at 44 weeks. In Aim
we will test the hypotheses that HIV exposed uninfected (HEU) infants whose mothers have LTBI during
are sensitized to mycobacterial antigens in utero, develop immunologic memory to Mtb and
an altered response to BCG vaccination . For this aim we will perform detailed analyses of CD4 T cell
subsets as well as antigen specific intra-cellular cytokine memory response to RD-1 antigens
 and ESAT-6, a DosR latency antigen and to PPD by flow cytometry. In Aim 2 we hypothesize that
factors such as Ab to Mtb can influence the infant immune response . For this aim a systems
approach for biophysical and functional characterization of FcR binding Ab will be performed in
plasma at delivery and infant plasma at weeks 12 and 44, for ascertaining longevity of passively
maternal Ab. Cytokine profile, country of origin, and IPT during pregnancy will be included in
analysis of maternal-infant immunity. In Aim 3 we hypothesize that infants diagnosed with LTBI in the
year of life have distinct gene transcriptomic profiles in monocytes and antigen specific CD4+ T cells
to those who are not infected with TB . In this aim we will profile CD4 T cells and monocytes
single cell transcriptomics. Transcriptional profiles will be correlated with immunologic profile by flow
and Ab profile by systems serology described in Aims 1 and 2 These studies are relevant for
immunological mechanisms of maternal-infant interaction in the context of LTBI in HIV+
and their EUI, and impact on BCG vaccine responses. Importantly they have the potential to
sensitive...

## Key facts

- **NIH application ID:** 9844060
- **Project number:** 5R01AI142669-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Savita Pahwa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $615,772
- **Award type:** 5
- **Project period:** 2019-01-05 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844060

## Citation

> US National Institutes of Health, RePORTER application 9844060, Immune correlates of LTBI in HIV-exposed infants (5R01AI142669-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9844060. Licensed CC0.

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