# Mapping and dissecting the role of antibodies in Mtb control

> **NIH NIH R56** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $815,165

## Abstract

While a quarter of the world carries the burden of tuberculosis, emerging data suggests that those
coinfected with HIV are at an elevated risk of reactivating the disease. However, the specific
immunological perturbations that lead to loss of Tb control are poorly understood. One critical risk
factor associated with HIV coinfection is the depletion of CD4 T cells, which has been linked to
increased Mycobacterium tuberculosis (Mtb) uptake into macrophages and diminished granuloma
integrity. However, even with the restoration of CD4 T cells with HAART, Mtb/HIV co-infected
individuals continue to exhibit a higher risk of Mtb reactivation. However, CD4+ T cell
loss/perturbations may also contribute to loss of Mtb containment through indirect mechanisms
such as the loss of the requisite help to B cells required for the production of highly functional
antibodies. Along these lines, mounting data point to an enrichment of anti-microbial antibody
responses among latently infected individuals, able to contain bacterial growth in vitro and even
control bacteria in vivo when transferred to mice prior to challenge. Thus, given our emerging
appreciation for a role for antibodies in Mtb-control/killing, here we propose to use a systems
serology profiling approach, to begin to define the specificities and functions of antibodies that
contribute to longitudinal control of Mtb in both HIV uninfected and infected populations.
Moreover, linked to B cell cloning, Fc-engineering, and in vitro/in vivo models, we also seek to
divorce humoral biomarkers of Mtb control from mechanistic roles of antibodies in preventing
progression to TB. Collectively, these data will provide novel insights into the potential humoral
profiles that if harnessed via vaccination or through therapeutics may lead to enhanced control of
Mtb.

## Key facts

- **NIH application ID:** 10234399
- **Project number:** 1R56AI155149-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Galit Alter
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $815,165
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234399

## Citation

> US National Institutes of Health, RePORTER application 10234399, Mapping and dissecting the role of antibodies in Mtb control (1R56AI155149-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10234399. Licensed CC0.

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