# Project 4: The intersection of innate and adaptive immunity to M. tuberculosis

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $414,106

## Abstract

Project Summary/Abstract (Project 4, Stanley)
Infection with Mycobacterium tuberculosis continues to be a leading cause of death worldwide. Efforts to
combat the tuberculosis pandemic are hampered by the lack of an effective vaccine. Vaccines against Mtb and
other intracellular pathogens that require cell-based immunity for control have been difficult to develop, in part
due to the limited number of adjuvants that elicit effective cell-based immunity. We recently reported that that
STING-activating cyclic dinucleotides (CDNs) formulated in a protein subunit vaccine elicit long-lasting
protective immunity to Mycobacterium tuberculosis in the mouse model. The efficacy of CDN adjuvanted
vaccines is dramatically improved when the vaccine is delivered via a mucosal route. Here we propose to
perform an in-depth characterization of the immune response to CDN adjuvanted protein subunit vaccines for
tuberculosis. First, we will determine how STING activation results in the development of protective immunity,
using knockout mice to dissect the contribution of the different outputs of STING signaling. Second, we have
found that the efficacy of vaccination with CDN is dependent on IL-17, however the mechanisms underlying the
protective efficacy of IL-17 are unknown. We will determine how IL-17 impacts the vaccine elicited immune
response, which CD4 Th17 subsets are most important, and which cell types in the lung respond to IL-17.
Finally, we test CDN adjuvanted protein subunit vaccines in heterologous prime boost regimens designed to
elicit complementary immune responses using recombinant BCG and Listeria monocytogenes strains
developed by the Cox (Project 2) and Portnoy (Project 1) labs. If successful, this project will uncover novel
mechanisms by which vaccines can elicit protective immunity to TB, and will exploit this knowledge to identify
vaccination regimens with enhanced efficacy.

## Key facts

- **NIH application ID:** 10400185
- **Project number:** 5P01AI063302-19
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Sarah A Stanley
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $414,106
- **Award type:** 5
- **Project period:** 2004-09-30 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400185

## Citation

> US National Institutes of Health, RePORTER application 10400185, Project 4: The intersection of innate and adaptive immunity to M. tuberculosis (5P01AI063302-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10400185. Licensed CC0.

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