# Mechanisms of anti-fungal Vaccine immunity

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $553,347

## Abstract

ABSTRACT
This competing renewal exploits a conserved fungal antigen to vaccinate against the three major systemic my-
coses of North America, Blastomycocis, Coccidiodomycosis and Histoplasmosis, and elucidate the mechanics
that underpin vaccine induced CD4 T cell memory immunity elicited against these pulmonary fungal infections.
While host resistance against respiratory pathogens is thought to reside with lung tissue-resident memory cells
(Trm) and mucosal immunity, our strong preliminary data unexpectedly reveal that systemic vaccination elicits
a population of migratory T cells that confer protection, whereas Trm elicited at the lung mucosa do not protect.
We have discovered a novel fungal ligand for dectin-2, Blastomyces endoglucanase 2 (Bl-Eng2), that is an ad-
juvant and an immune-dominant antigen that confers vaccine immunity. We have also developed MHCII: pep-
tide tetramers to enable in vivo tracking of Eng2-specific migratory and lung-resident CD4 T cells. Importantly,
Eng2 is conserved Blastomyces, Coccidiodes and Histoplasma, the agents of endemic mycoses. We propose
to identify Eng2 T cell epitopes that confer protection against the endemic mycoses and uncover correlates of
protective immunity during the systemic vaccine priming and effector phases. We hypothesize that migratory
T cells confer vaccine immunity by homing to lung via CX3CR1 and CXCR3 mediated chemotaxis. We aim to:
 1. Elucidate the role of migratory T cells and their homing receptors in vaccine resistance. We will use
adoptive transfer, parabiosis and SIPR1 blockade of T egress from the SLO to identify the functional and
phenotypic features of protective CD4 T cells and determine the roles of CX3CR1 and CXCR3 in migration.
2. Pinpoint priming events that elicit protective, migratory T cells. We will identify accessory cells that
transport Eng2 to the lymph nodes, display peptide and prime naïve T cells, and define by fate mapping of
T cells whether phenotypes are irreversibly set locally in draining LN or display plasticitity on recall to lung.
3. Identify Eng2 T cell epitopes that protect mice against infection and are recognized by humans. We will
 use an immunoinformatic algorithm to identify Eng2 T cell epitopes that protect C57BL6 and “humanized”
 HLA-DR4 mice against the endemic mycoses and are recognized by humans recovered from the diseases.
Our work will exploit a conserved fungal antigen to vaccinate against multiple systemic mycoses. We will use
this vaccine to unveil conceptually new insight about how antifungal CD4 T cells are ideally primed systemi-
cally, and divine the mechanics by which they migrate to resist pulmonary infection. Our work will challenge
emerging views about a critical role for Trm in the generation of mucosal resistance to respiratory infection.

## Key facts

- **NIH application ID:** 9938388
- **Project number:** 5R01AI040996-21
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** BRUCE Steven KLEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $553,347
- **Award type:** 5
- **Project period:** 1997-05-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938388

## Citation

> US National Institutes of Health, RePORTER application 9938388, Mechanisms of anti-fungal Vaccine immunity (5R01AI040996-21). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9938388. Licensed CC0.

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