# Biomarkers to Stratify Risk of Progression from Latent TB Infection to Active

> **NIH NIH U19** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $661,749

## Abstract

The currently available tuberculin skin test (TST) and interferon gamma release assays (IGRA) cannot
distinguish between infected persons who i) contain the infection and eliminate the organism ("self-cure"); ii)
contain the organism but allow it to persist in a non-replicating state, providing a focus for future reactivation
disease (truly "latent infection"); iii) contain the infection, which progresses to clinical disease within the first
few years after infection ("progressive infection"). These three subpopulations of infected persons are
grouped together as "latent TB infection" (LTBl). Biomarkers that differentiate among the three outcomes
would allow targeting of preventive therapy to those most likely to benefit, facilitate development of new
drugs active against specific stages of infection and promote durable cure. Predictive biomarkers are most
needed for household contacts (HHC) of patients with infectious pulmonary TB (PTB), as they have the
highest risk of developing active disease and, therefore, are an important focus for TB prevention programs.
In Aim 1, we will employ FDG-PET/CT to characterize the early events in lymph node (LN) and lung following
Mtb infection and apply the findings to guide the discovery of blood biomarkers predictive of high risk of
progression to disease. In Aim 2 we will use multi-parametric flow technology and Cytokine Fingerprinting, a
computational method for analysis of high-dimensional cytometric data, to derive a signature profile of
effector and memory T cell subsets in treated HHC to discover biomarkers predictive of low risk of
progression to disease and cure. The biomarkers of cure characterized in newly-infected individuals treated
with isoniazid (INH) will guide identification of individuals that eradicate infection spontaneously (self-cure).
Although memory T cells will be phenotypically similar in the drug-cured and self-cured individual,
functionally they may differ since self-cured individuals achieved the status through immunity. In Aim 3,
antigen-specific T cells from self-cured individuals will be identified by tetramers to discover correlates of
protection. The proposed study will provide a new paradigm for TB prevention by facilitating specific
treatments for populations at greatest risk for developing TB.

## Key facts

- **NIH application ID:** 10004560
- **Project number:** 5U19AI111276-08
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** David Alland
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $661,749
- **Award type:** 5
- **Project period:** 2014-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004560

## Citation

> US National Institutes of Health, RePORTER application 10004560, Biomarkers to Stratify Risk of Progression from Latent TB Infection to Active (5U19AI111276-08). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10004560. Licensed CC0.

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