# Epitope validation of fungal allergens in severe asthma

> **NIH NIH U19** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2021 · $397,180

## Abstract

PROJECT SUMMARY
In this application, we will characterize CD4 T cells reactive to epitopes of the fungal allergens Aspergillus
fumigatus (ASP) and Alternaria alternata (ALT) to understand the molecular basis of severe asthma.
Sensitization and/or exposure to antigens (spores) from fungal species such as ASP and ALT have been
strongly associated with risk for a number of asthma-severity-related adverse outcomes. Based on this
premise, we will test the hypotheses that (i) Fungal allergen-specific CD4 T cells are more pathogenic and
qualitatively different when compared to allergen-specific CD4 T cells directed towards non-fungal inhaled
allergens such as house dust mite (HDM), cockroach (CR), mouse (MO) or potential oral allergens such as
cow milk (CM). (ii) Fungal allergen-epitope-specific CD4 T cells in patients with severe asthma have more
pathogenic features than those from mild asthmatics. We will capitalize on subjects enrolled in three large
asthma cohorts for these studies.
In Aim 1, we will define epitopes recognized by Aspergillus (ASP) and Alternaria (ALT)-sensitized asthmatics
categorized based on disease severity. The reactivity of predicted ASP and ALT epitopes will be tested in 20
sensitized subjects with mild and severe asthma and in 20 non-sensitized subjects without asthma to assess
the nature of allergic versus healthy responses. By comparing the epitope-reactivity of the three cohorts, we
will define epitopes that are common or specific to each subgroup: severe asthma, mild asthma and non-
sensitized non-asthmatics. In Aim 2, we will determine the molecular profile of fungal (ASP and ALT)-specific
CD4 T cells in patients with different asthma severity. We will utilize fungal epitope mega-pools to define the
phenotype and transcriptional profile (at bulk and single-cell level) of ASP and ALT epitope-specific CD4 T cell
responses in 10-20 fungal-sensitized subjects with severe and mild-to-moderate asthma, allergic
bronchopulmonary aspergillosis (ABPA) and in control subjects without asthma. In parallel, we will also assess
the molecular profile of fungal-specific CD4 T cells present in the airways of asthmatic subjects. To determine if
the molecular features of fungal allergen-specific CD4 T cells are different from allergen-specific CD4 T cells
directed to HDM, CR, MO, CM or antigen-specific Th2 cells induced by vaccination (pertussis and tetanus), we
will perform additional transcriptomic analysis of these cells, and through the integrated Data Management
Core specializing in bioinformatics cross compare data sets with Project 1 and 2. Together these fungal
epitope validation studies in subjects with varying asthma severity will provide insights into the nature of CD4 T
cell responses that drive pathogenesis of severe asthma.

## Key facts

- **NIH application ID:** 10083712
- **Project number:** 5U19AI135731-04
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Pandurangan Vijayanand
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $397,180
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083712

## Citation

> US National Institutes of Health, RePORTER application 10083712, Epitope validation of fungal allergens in severe asthma (5U19AI135731-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10083712. Licensed CC0.

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