# Regulation of vaccine-induced anti-fungal Th17 cells

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $560,484

## Abstract

Project Summary/Abstract
Vaccines against infectious diseases have been hailed as the greatest achievement in public health over the
last century. This competing renewal will investigate a novel adjuvant that elicits cellular immune responses
needed for better vaccines. The lack of an appropriate adjuvant is one major barrier to developing a safe and
effective vaccine against infections with fungal pathogens, which represents an unmet need in medicine and
public health. Despite the rising rates of severe fungal infections, no vaccines against fungi are commercially
available. While current vaccines against infectious diseases preferentially induce production of antibodies,
their contribution to host defense against fungi is limited. Cellular immunity is essential for the resolution of
fungal infections. Vaccine-induced resistance against fungi in experimental models requires Th17 and Th1
cells that produce IL-17 and IFN-γ and mediate protection in part by recruiting and activating phagocytes to
augment killing of fungi. In the last funding cycle, we discovered that fungal recognition by the C-type lectin
receptor (CLR) Dectin-2 is required for the differentiation of protective Th17 and Th1 cells against dimorphic
fungi. Through biochemical purification and mass spectrophotometry analysis, we identified a novel bona-fide
fungal ligand for Dectin-2, the glycoprotein Blastomyces Eng3 (Bl-Eng3).
In this application, we propose to characterize and functionally test Bl-Eng3 as an adjuvant for vaccination
against fungi. We hypothesize that Bl-Eng3 activates dendritic cells, drives differentiation of antigen
(Ag)-specific Th17 and Th1 cells, and thereby promotes protective cellular immunity against fungal
infection. We also posit that the protein backbone and glycan modifications account for ligand activity
and that Bl-Eng3 will be an effective adjuvant alone or together with other CLR ligands for vaccines
against fungi. We provide strong preliminary data to support our hypotheses. Using Dectin-2 reporter cells,
we have established an in vitro screening system to dissect the contributions of the protein backbone and its
glycosylation to Dectin-2 ligand activity and an in vivo adoptive transfer system to delineate the effects of the
ligand adjuvant on the differentiation of naïve antigen-specific CD4+ T-cells into protective Th17 and Th1 cells.
Our approach offers a powerful complimentary strategy that will identify the ligand moiety of the glycoprotein in
aim 1, assess adjuvancy for the maturation and priming of Ag-presenting cells (APCs) and Ag-specific T cells
in aim 2, and determine receptor collaboration with other CLRs and protective efficacy in experimental models
of pulmonary and systemic fungal infections in aim 3. Our work will provide new insight needed to promote the
maturation of APCs and differentiation of protective Th17 and Th1 cells. This knowledge will provide the basis
for developing and designing new vaccine strategies against fungi, a...

## Key facts

- **NIH application ID:** 9976397
- **Project number:** 5R01AI093553-09
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Marcel Wuethrich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $560,484
- **Award type:** 5
- **Project period:** 2011-05-03 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976397

## Citation

> US National Institutes of Health, RePORTER application 9976397, Regulation of vaccine-induced anti-fungal Th17 cells (5R01AI093553-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9976397. Licensed CC0.

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