# Immune Correlates of Protection from TB

> **NIH NIH R01** · TEXAS BIOMEDICAL RESEARCH INSTITUTE · 2022 · $889,259

## Abstract

Abstract. Since TB remains an infection that results in extensive mortality, efficacious vaccines against Mtb
infection are urgently sought. Recently, it has been proposed that mycobacteria attenuated in the regulation of
redox-stress may be effective vaccine candidates, since these could interfere with the production of several
microbial antioxidants. We have recently shown that an isogenic Mtb mutant in stress-response factor SigH
significantly and impressively protects against homologous Mtb infection if used to immunize macaques via the
aerosol route.
As part of this application we propose to better understand correlates of protective immunity upon mucosal
vaccination with sigH, using a set of three specific aims that are not inter-dependent. In addition we will study
if such vaccination can also protect against infection with highly infectious heterologous strains of Mtb (Specific
Aim 1). In a series of mechanistic experiments, we will deplete B-cells recruited to the lung iBALT follicles in
great numbers following vaccination with the sigH mutant, using a recently developed and optimized
macaque-specific reagent. These animals will be concurrently challenged with a high-dose homologous Mtb
challenge to assess if the protective efficacy of sigH is eviscerated in the absence of B-cells (Specific Aim 2).
Finally, we will study if inducible bronchus associated tissue (iBALT) provides a sanctuary where SIV can
persist, or whether iBALT protects Tfh cells from depletion by SIV during co-infection (Specific Aim 3).
Together the results obtained as part of these three aims will i) have the potential to establish sigH as a
leading live-mycobacterium anti-TB vaccine vehicle; ii) provide defining correlates of protection from TB in a
model system which would provide immediate applicability in human trials; and iii) define the controversial role
of B-cells in protection from TB.

## Key facts

- **NIH application ID:** 10197794
- **Project number:** 5R01AI134240-05
- **Recipient organization:** TEXAS BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** Deepak Kaushal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $889,259
- **Award type:** 5
- **Project period:** 2017-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197794

## Citation

> US National Institutes of Health, RePORTER application 10197794, Immune Correlates of Protection from TB (5R01AI134240-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10197794. Licensed CC0.

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