# Mucosal Adjuvant to Induce Multipronged T Cell Immunity to Tuberculosis

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $232,500

## Abstract

Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb) kills more people in the world,
than any single infectious disease. The only approved vaccine for TB, the Bacilli Calmette-Guerin (BCG) provides
protection against miliary and meningeal TB in children, but is NOT effective against pulmonary TB in adults, the
most transmissible and prevalent form of the disease. Therefore, BCG vaccination has not thwarted the global
epidemic of TB, and developing an effective TB vaccine ranks at the top among the current global health priorities.
 Mtb is a complex and highly adapted slow-growing organism and protection against TB will likely require
multiple layers of immune defense that counter the pathogen’s growth and spread at multiple steps in its life
cycle and different phases of the disease. Accumulating evidence suggests that a critical number of strategically
positioned(Tissue resident [TRM], effector [TEM] and central [TCM] memory) and functionally diverse (TC1/TH1 and
TC17/TH17) subsets of memory CD4 and CD8 T cells will be required to collectively provide effective defense
against pulmonary TB. However, several of the current vaccines that are in preclinical or clinical stages of
development are skewed towards inducing only TEM/TCM TH1 cells, which might be necessary but not sufficient
to provide effective protection against pulmonary TB. We have identified a mucosal vaccine combination
adjuvant consisting of a carbomer-based adjuvant, AdjuplexÒ (ADJ) and a TLR-4 agonist, glucopyranosyl lipid
A (GLA) that elicits a multipronged immunity consisting of high numbers of mucosally imprinted (TRM) and
circulating (TEM and TCM) subsets of memory CD4/CD8 T cells that produce IFN-g and/or IL-17 in lungs. These
exciting preliminary data underpinned the central hypothesis that a subunit vaccine consisting of ADJ+GLA
and immunogenic TB antigens (Ag85B [early antigen], ESAT-6 [replicating] and Rv2660c [latency
antigen]) will induce broad T cell-mediated immunity that protects against pulmonary TB. The specific
aims are to test the hypothesis that: (1) mucosal imprinting of TRM, differentiation of TCM and TEM and functional
programming of TB-specific memory CD4 and CD8 T cells are dictated by the adjuvant and the route of vaccine
administration and not by the antigen; (2) vaccines that elicit functionally diverse (TC1, TC17, TH1 and TH17) TRM,
TEM and TCM will provide effective immunity to pulmonary TB.
 This exploratory R21 proposal exploits the complementary expertise of two PIs: Dr. Suresh (T cell
memory) and Dr. Talaat (TB pathogenesis and vaccines). This project is highly significant because it may lead
to the development of a safe and effective subunit vaccine against pulmonary TB. The innovation of this project
stems from the preclinical development of a novel combination adjuvant that elicits a potent T cell response with
unprecedented phenotypic and functional diversity in the lungs. Overall, this low risk-high pay off exploratory
proj...

## Key facts

- **NIH application ID:** 9997313
- **Project number:** 1R21AI149793-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Marulasiddappa Suresh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $232,500
- **Award type:** 1
- **Project period:** 2020-03-12 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997313

## Citation

> US National Institutes of Health, RePORTER application 9997313, Mucosal Adjuvant to Induce Multipronged T Cell Immunity to Tuberculosis (1R21AI149793-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9997313. Licensed CC0.

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