# Development of a multivalent vaccine against Coccidioides infection

> **NIH NIH R01** · UNIVERSITY OF TEXAS SAN ANTONIO · 2022 · $378,328

## Abstract

Project Summary
Coccidioidomycosis affects residents in the southwestern United States, northern Mexico and scattered areas
of South America. An estimated 150,000 people in the United States become infected with Coccidioides
annually. There is an urgent unmet need to develop better chemotherapies and a vaccine against Coccidioides
infection. This proposed study is to optimize protective efficacy and delineate immune mechanisms of a newly
developed multivalent vaccine against coccidioidomycosis. The vaccine consists of a recombinant chimeric
polypeptide antigen (rCPA2) composed of the most immunogenic fragments of 4 previously identified
Coccidioides antigens and 5 predicted T-cell epitopes. Preliminary studies demonstrate robust and long-lasting
adaptive T-cell responses following vaccination of human MHC II-expressing HLA-DR4 transgenic mice with
glucan-chitin particles (GCPs) “loaded” with rCPA2. Furthermore, optimized GCP-rCPA2 vaccine affords the
best protective efficacy among 5 tested adjuvant formations and comparable to a live, attenuated ΔT vaccine.
The rCPA+GCP vaccine is well processed by macrophages and dendritic cells at the vaccination sites and
mediates differential immune gene expressions leading to enhanced antigen presentation and Th1- and Th17-
mixed polarization. Th17 immunity has shown to be indispensable for vaccine immunity against
coccidioidomycosis. The central hypothesis of this proposal is that an optimized rCPA2 antigen loaded in
GCP adjuvant/delivery system with an FDA-approved carrier can elicit a broad spectrum of protective immunity
for humanized mice against infection with both species of Coccidioides. The goal is to investigate the
protective mechanisms of the optimized GCP-rCPA2 vaccine using humanized murine models of
coccidioidomycosis and human immune cells. There are 3 Specific Aims: Aim 1 is to create an optimized
rCPA2 that can induce a broad spectrum and durable protective immunity against both species of
Coccidioides. Human T-cell epitopes on rCPA2 will be mapped for 3 common human MHC II alleles. There is
considerable morphological and genomic diversity among different isolates of C. posadasii and C. immitis. The
optimized antigen will include dominant epitopes derived from both species of Coccidioides for multiple HLA
alleles. Protective efficacy of the optimized vaccine will be tested to against two selected isolates of each
Coccidioides species that present with the least homology of the antigens. Aim 2 is to optimize the GCP
adjuvant formulation for eliciting a protective Th1- and Th17-mixed response against Coccidioides infection
using both human and mouse APCs and CD4+ T cells. An optimized GCP adjuvant/delivery system will be
created to maximize protective efficacy. Aim 3 To study the vaccine induced protective mechanism that guides
Th1 and Th17 responses using murine models of coccidioidomycosis. Upon completion of this project an
optimized and protective GCP2-rCPA2 vaccine will be identified for...

## Key facts

- **NIH application ID:** 10399515
- **Project number:** 5R01AI135005-05
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** CHIUNG-YU HUNG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $378,328
- **Award type:** 5
- **Project period:** 2018-05-08 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399515

## Citation

> US National Institutes of Health, RePORTER application 10399515, Development of a multivalent vaccine against Coccidioides infection (5R01AI135005-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10399515. Licensed CC0.

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