# Multiplexed Antigen-Specific Antibody Fc Profiling on a Chip for Point-of-Care Diagnosis of TB in HIV-infected Children

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $974,009

## Abstract

Abstract:
Tuberculosis (TB) is a leading cause of death in children, with an estimated 1 million children
affected, and more than 200,000 deaths in children yearly due to TB. HIV coinfection has been
estimated to contribute to more than 35% of TB-related deaths in children in Africa, making the
collision of the HIV and TB epidemics one of the most lethal to date. Both HIV infection as well as
HIV-exposure in utero, among HIV-exposed but uninfected (HEU) children, have been linked to
higher risks for the development of TB among young children. Failures to prevent TB disease and
devastation has been attributed to the lack of an effective vaccine as well as our inability to
diagnose children under the age of 5 due to the difficulty in obtaining sputum and the
paucibacillary nature of the disease in young children. Thus, an inexpensive biomarker-based
diagnostic test tailored for pediatric TB using non-sputum samples that could be used at
the point of care in resource-limited settings could profoundly improve TB treatment and
prevent deaths in children, especially in those under 5 years of age. While Mtb-specific
antibody titer-based diagnostics have performed poorly in the past, due to the inability of
accurately distinguishing between active TB disease from latent TB infection (LTBI), recent data
from our group has shown that Mtb-specific antibody glycosylation shifts significantly across
disease states. Moreover, this antigen-specific antibody glycosylation approach reliably classifies
individuals into active and latent disease states across HIV infection status, across geographies
and can even distinguish recent Typhoid infection among children in endemic areas. Based on
these observations, a simple binding-based assay was developed that can rapidly, sensitively,
and specifically detect changes in Mtb-specific antibody glycosylation from a small sample volume
offering an opportunity for the first time to develop an antigen-specific antibody glycosylation
diagnostic for pediatric TB from a microliter-scale sample. Given that HIV+, HEU, or
unexposed children may target distinct Mtb antigens, here we have assembled a multi-disciplinary
team and program termed FASTER-Kids (Fc Antibody Signatures for TubERculosis in children)
that will: 1) Define the landscape of Mtb-specific antibody glycosylation responses that distinguish
children with TB, 2) Develop a point-of-care test that will rapidly capture these specific antibody
responses and glycosylation changes from microliters of blood. Ultimately, this collaborative
structure will enable the iterative improvement and development of this simple, rapid, inexpensive
diagnostic to manage TB infection in young children.

## Key facts

- **NIH application ID:** 9986268
- **Project number:** 1R01AI152158-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Galit Alter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $974,009
- **Award type:** 1
- **Project period:** 2020-05-06 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986268

## Citation

> US National Institutes of Health, RePORTER application 9986268, Multiplexed Antigen-Specific Antibody Fc Profiling on a Chip for Point-of-Care Diagnosis of TB in HIV-infected Children (1R01AI152158-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9986268. Licensed CC0.

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