# Serological Biomarkers for Coccidioidomycosis

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2024 · $378,234

## Abstract

PROJECT SUMMARY
 As of 2017, coccidioidomycosis (Cocci) also known as Valley Fever (VF) was designated a reportable
disease in 22 states (1). The majority of the cases in the US occur in southern Arizona and California where the
population is increasing with influx of naïve individuals, in particular, elderly retirees. Since Coccidioides sp, can
cause significant morbidity and mortality in fully immunocompetent hosts, this represents an important threat to
these regions where >10% percent of the US population resides, not including substantial tourist or part-time
resident populations in Arizona and California. Importantly, the reporting criteria require a positive laboratory
test for inclusion, yet ~50% of patients–who will eventually test positive–test negative while acutely ill (2). Testing
has low sensitivity and specificity leaving sick patients and their health care providers without an accurate
diagnosis. Thus, there is a profound need for better diagnostic approaches to properly identify Cocci patients to
ensure appropriate follow-up and therapy ensues.
 Coccidioides spp. grow as mycelia in the desert soils and produce spores (arthroconidia) to survive during
times of adverse growth conditions. When this soil is disturbed, arthroconidia aerosolize and are inhaled to
initiate infection. Inside the host, the spores transform into spherules containing endospores which grow in the
lung. When spherules burst, endospores, are released and can each disseminate to form a new spherule.
 Clinical diagnosis is difficult because patients’ symptoms resemble other bacterial and viral pneumonias.
Laboratory diagnosis often relies solely on serology, but ~50% of patients do not test positive while they are
acutely ill which results in inaccurate diagnosis an inappropriate treatment. We propose that it is time for a re-
evaluation of seroreactive coccidioidal antigens. For the past six decades, serologic diagnosis of
coccidioidomycosis has relied on IgM responses to tube precipitin (TP) and IgG responses to complement
fixation (CF) antigens. Since these antigens are primarily expressed in mycelia, not in spherules which is the
fungal form that grows in the host, it is not surprising that many patients are seronegative because they have not
yet generated antibodies to spherule antigens during acute pulmonary illness.
 The GOAL of this proposal is to identify new coccidioidal antigens that react with acutely infected patient
sera. The objectives are to utilize the recently published Coccidioides spp. proteome to create a nucleic acid
programmable protein array (NAPPA) in which every coccidioidal protein is screened for reactivity with VF patient
sera. Our hypothesis is that this survey of the Coccidioides proteome will reveal new spherule-phase antigens
that are reactive with more patients, especially acutely ill patients who are seronegative for TP and/or CF
antigens. Once we identify a small panel of seroreactive antigens, they can be incorporated into ex...

## Key facts

- **NIH application ID:** 10844516
- **Project number:** 5R01AI155954-04
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** DOUGLAS F. LAKE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $378,234
- **Award type:** 5
- **Project period:** 2021-06-07 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844516

## Citation

> US National Institutes of Health, RePORTER application 10844516, Serological Biomarkers for Coccidioidomycosis (5R01AI155954-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10844516. Licensed CC0.

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