# SigH based attenuated, efficacious Mtb vaccines to protect against lethal TB

> **NIH NIH R01** · TEXAS BIOMEDICAL RESEARCH INSTITUTE · 2021 · $877,748

## Abstract

Abstract
Infection with M. tuberculosis (Mtb) can cause TB, which is now the leading global cause of
mortality due to a single infectious disease agent. The failure to control TB stems from the lack of
an effective vaccine. BCG, the vaccine currently in use, is unable to generate long-lived memory
responses and protect against pulmonary TB in adults. New vaccines against TB are therefore,
urgently needed. Our work has shown that the ΔsigH mutant of Mtb is attenuated for replication
and disease in macaques). Aerosol vaccination with this mutant induces strong lung immune
signatures that protect against lethal TB. Nonpathogenic ΔsigH infection in macaques is not
reactivated by SIV co-infection. Additional unrelated mutation(s) are however needed in ΔsigH
to ensure its complete attenuation. This project aims to develop a ΔsigH -based human TB vaccine
candidate that could eventually advance to clinical development. ΔsigH deletion will be added to
10 recombinant Mtb strains. Some of these mutants generate immune enhancement- or
auxotrophy-based attenuation phenotypes, while others render Mtb avirulent in macaque lungs.
We will assess the safety of these ten strains in SCID mice and progressively smaller numbers in
immunocompetent and SIV co-infected macaques by multiplexing. Two strains that consistently
provide the best results in terms of safety/immunogenicity will be evaluated in detail for
immunogenicity and efficacy via aerosol (AER) vaccination relative to BCG- and ΔsigH -
vaccination, in a physiologically relevant macaque model.

## Key facts

- **NIH application ID:** 10162489
- **Project number:** 5R01AI138587-04
- **Recipient organization:** TEXAS BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** Chinnaswamy Jagannath
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $877,748
- **Award type:** 5
- **Project period:** 2018-05-17 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162489

## Citation

> US National Institutes of Health, RePORTER application 10162489, SigH based attenuated, efficacious Mtb vaccines to protect against lethal TB (5R01AI138587-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10162489. Licensed CC0.

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