# Defining adaptive immune responses to Mtb-infection and TB disease among young children with and without HIV-exposure

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $713,830

## Abstract

PROJECT SUMMARY
Tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb) is a leading cause of morbidity and
mortality in young children <5 yr old. The vulnerability of young children to develop TB following primary infection
is not understood; this critical knowledge gap hampers efforts to develop a more effective vaccine and improved
diagnostic tests for this high-risk population. HIV-exposed (HEU) children are the majority of children living in the
homes of HIV+ adults, where they are more likely than HIV-unexposed-uninfected (HUU) children to be TB
exposed. Clinical, epidemiologic, and immunologic findings support that young, HEU children will exhibit
distinctive immune responses following Mtb-exposure; however, immune responses to Mtb-infection have not
been characterized in this high-risk population. Our proposal will comprehensively define adaptive immune
responses to Mtb-exposure and TB in children < 5yr using a pediatric TB household contact (HHC) study based
in Kampala, Uganda, where up to 20% of children are HEU. Our approach will identify unique immunologic
biosignatures driven by where the child sits on the TB disease spectrum, as well as by HIV-exposure status. We
hypothesize that immune biosignatures of Mtb-exposed asymptomatic HEU children will more closely resemble
those observed among children with TB, as compared to asymptomatic HUU children. If proven, this would
suggest that Mtb-exposed HEU children are more likely to be experiencing a pre-clinical rather than quiescent
or latent Mtb-infection. Such findings would have implications for the development of immune-based diagnostics
for Mtb-infection and TB disease that may perform differently in HIV-exposed and unexposed children, as well
as clinical management and monitoring of HEU-children following TB exposure. Working with a biorepository of
samples obtained from Ugandan children < 5 yr, and a proposed prospective cohort of Ugandan children < 5 yr
who are TB HHC, we will address three specific aims that: 1) define longitudinal, functional and phenotypic Mtb-
specific adaptive immune responses among young children who developed TB or remained asymptomatic; 2)
develop a pool of novel Mtb-epitopes and focused flow cytometry-based assay customized to detect Mtb-specific
T cell responses in young children; and 3) establish a unique Mtb-specific antibody Fc profile that defines children
with TB. Our proposal will advance pediatric global health by: 1) identification of immunologic signatures
reflecting successful containment of primary Mtb infection that can serve as correlates of protective immunity for
novel vaccine trials; 2) development of novel blood-based assays that discriminate between young children with
TB and those whom have been exposed but successfully contained their infection.

## Key facts

- **NIH application ID:** 10835001
- **Project number:** 5R01AI157807-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Christina Louise Lancioni
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $713,830
- **Award type:** 5
- **Project period:** 2021-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835001

## Citation

> US National Institutes of Health, RePORTER application 10835001, Defining adaptive immune responses to Mtb-infection and TB disease among young children with and without HIV-exposure (5R01AI157807-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10835001. Licensed CC0.

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