# Role of IL-17 in Protective Vaccine-induced Immune Responses Against Tuberculosis

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $567,793

## Abstract

PROJECT SUMMARY
Mycobacterium tuberculosis (Mtb) latently infects one-fourth of the world’s population, causing pulmonary
tuberculosis (TB) in ~9 million people and resulting in ~1.3 million deaths each year1. The currently available
TB vaccine, Mycobacterium bovis BCG (BCG), shows variable efficacy. In addition, Multi-Drug-Resistant
(MDR) Mtb strains have recently emerged. Thus, there is a great need for new TB vaccines2. Studies in the
past decade have mainly utilized induction of T helper cell type 1 (Th1) responses and the production of the
cytokine, Interferon-gamma (IFNγ), as readout for vaccine efficacy against TB3. Our studies during the prior
funding period demonstrated that Interleukin (IL)-17 and T helper type 17 (Th17) vaccine responses are critical
for vaccine-induced immunity against TB4-6. Importantly, we recently demonstrated that mucosal vaccination
with the Mtb antigen with Th17-inducing adjuvants induced potent lung-resident Th17 cells and improved BCG
vaccine-induced protection following Mtb challenge4,6-8. Our mechanistic studies demonstrated that IL-17-
induced chemokines, including CXCL-136,9-11, localize CXCR5-expressing T cells near Mtb-infected
macrophages, resulting in the formation of lung lymphoid follicles and activating macrophages to mediate Mtb
control5,12. Despite these major advances in understanding the role of Th17 vaccine-induced cells in TB, our
data show that upon Mtb infection, the accumulation of vaccine-induced Th17 immune responses in the lung is
not accelerated enough to provide “sterilizing” immunity or complete Mtb control5. In exciting new data
generated during the prior funding cycle, we show that we can overcome this bottleneck by using Dendritic Cell
(DC) based therapy by either activating endogenous DCs, or transfer of exogenously activated DCs into
vaccinated hosts, to achieve superior Mtb control6,13. Thus, the work proposed in this R01 renewal builds on
these important and highly relevant findings with three Specific Aims: Specific Aim 1. Identifying the early
cytokine pathways that modulate APC function to promote Th17 responses and induce superior immunity
against TB. Specific Aim 2. Identifying the IL-23 and IL-17-dependent mechanisms that mediate early Th17
responses and Mtb control. Specific Aim 3. Identification of novel C-type lectin receptor agonists as Th17-
inducing TB vaccines. The emergence of extensively drug-resistant strains (XDR) of Mtb, for which no
treatments currently exist, makes the development of an effective TB vaccine incredibly urgent. The work
proposed in this grant will continue to significantly impact the design and use of future vaccine strategies by
allowing us to promote IL-17 responses to generate improved, long-term lasting vaccine-induced immunity
against TB.

## Key facts

- **NIH application ID:** 10755159
- **Project number:** 7R01HL105427-11
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Shabaana A. Khader
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $567,793
- **Award type:** 7
- **Project period:** 2010-12-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10755159

## Citation

> US National Institutes of Health, RePORTER application 10755159, Role of IL-17 in Protective Vaccine-induced Immune Responses Against Tuberculosis (7R01HL105427-11). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10755159. Licensed CC0.

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