# Antibody Mediated Mechanisms of Immune Modulation in Tuberculosis

> **NIH NIH K08** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $189,000

## Abstract

Project Summary/Abstract
This proposal presents a five year research career development program focused on the study of antibody
mediated immune modulation in tuberculosis to expand the breadth and depth of understanding the role of
humoral immunity in this disease. The candidate is currently an Instructor of Medicine at Harvard Medical
School in the Division of Infectious Diseases at the Massachusetts General Hospital. The outlined proposal
builds on the candidate's previous research and clinical experience in host pathogen interactions by integrating
two new domains of expertise represented by her mentor team of Drs Sarah Fortune and Galit Alter at the
Harvard School of Public Health and the Ragon Institute of MGH, MIT and Harvard: tuberculosis and antibody
mediated mechanisms of innate immune effector functions. The proposed experiments and didactic work will
position the candidate with a unique set of cross disciplinary skills that will enable her transition to
independence as a physician scientist in antibody mediated host pathogen interactions in tuberculosis.
One third of the world's population carries the burden of tuberculosis (TB). Efforts to reduce this burden have
been hindered by the lack effective diagnostics and a protective vaccine underpinned by gaps in the
understanding of the immune response in TB disease. While cellular immunity is important, the antibody (Ab)
or humoral landscape is poorly understood. Ab function is determined by the combination of antigen specificity
via the Fab and ability to recruit functional responses via the Fc domain. Ab Fc mediated recruitment of cellular
responses is a promising underexplored potential for immune control. The foundation for this proposal is based
on preliminary studies evaluating differences in antibody profiles from a systems serological approach in a
cohort of individuals with latent and active TB that suggest a potential protective role for antibodies in TB
disease. How exactly antibodies might function in this context and its physiological relevance are questions
that this proposal begins to address. More specifically, the aims of this proposal are 1: Define the antigen
specificity of functional M. tuberculosis (Mtb) specific antibodies, 2: Dissect the role for Fc/FcR mediated
intracellular Mtb restriction and 3: Identify the macrophage effector mechanisms through which Ab restrict
intracellular Mtb. The scientific objective of this proposal is to begin to define the Ab Fab and Fc features with
the capacity to mediate effector function against intracellular Mtb with the vision of targeted transition into an
appropriate animal model to generate hypotheses that inform the direction and design of subsequent human
studies to expand the repertoire for immune correlates/diagnostics and rational vaccine design.

## Key facts

- **NIH application ID:** 9872120
- **Project number:** 5K08AI130357-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Lenette Lu
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $189,000
- **Award type:** 5
- **Project period:** 2017-02-10 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872120

## Citation

> US National Institutes of Health, RePORTER application 9872120, Antibody Mediated Mechanisms of Immune Modulation in Tuberculosis (5K08AI130357-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872120. Licensed CC0.

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