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Fungal Infections and Studies / Bartonella Species Infections Research · Journal article
The Journal of Immunology · July 28, 2026
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This is an exploratory immunological study that uses TCR sequencing and antigen multiplexing to identify Coccidioides-specific T cell antigens and clones in naturally exposed humans and pig-tailed macaques. The work confirms some previously known antigens, identifies new ones, and establishes cross-species similarity in T cell responses, but provides no data on clinical efficacy, protection, or diagnostic utility. The authors propose to track these antigens in future challenge or vaccination studies to identify correlates of protection.
Comparative cross-species immunological study with antigen discovery. Naturally exposed pig-tailed macaques and Valley fever patients (humans); specific eligibility criteria, exposure history, disease severity, and prior treatment not detailed.. Intervention: Stimulation with overlapping peptide pools from 27 Coccidioides antigens. Compared with: Cross-species comparison between PTM and humans; comparison to previously known antigens and mouse protective DNA vaccination antigens.
Similar antigens were recognized by T cells in pig-tailed macaques and humans, validating the PTM model for Valley fever research Previously unknown Coccidioides antigens not previously associated with T cell immunogenicity were identified Th17 and Th1 immune responses and their associated T cell clones were characterized by single cell sequencing
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This work identifies potential vaccine or diagnostic antigens and supports use of pig-tailed macaques as a model for future efficacy studies, but does not yet demonstrate clinical utility or protection. Results require validation in challenge or vaccination trials to establish clinical relevance.
Exploratory antigen discovery and T cell characterization study in a model system with confirmation needed in clinical vaccination or challenge studies; no efficacy endpoint reported.
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This work identifies potential vaccine or diagnostic antigens and supports use of pig-tailed macaques as a model for future efficacy studies, but does not yet demonstrate clinical utility or protection. Results require validation in challenge or vaccination trials to establish clinical relevance.
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Abstract Introduction Coccidioidomycosis (Valley fever (VF)) is frequently misdiagnosed and mistreated as bacterial or viral pneumonia due to similar clinical presentations. Severe VF manifests in 5% of symptomatic cases and can be life-threatening. T cell responses play a vital role in vaccine-induced protection in mouse models and appear to be critical for resolution of infection in humans. We set out to identify T cell antigens and responses that are generated in pig-tailed macaques (PTM) and humans to aid antigen discovery and model development. Methods Peripheral blood mononuclear cells (PBMCs) were collected from both humans and PTM. The PBMCs were non-specifically expanded then stimulated with overlapping pools of Coccidioides-specific peptides from 27 antigens following an antigen multiplexing scheme. Activated T cells were sorted, T cell receptor (TCR) sequenced, and the TCR clonotypes were associated with the stimulating Coccidioides antigens. Specific T cell responses were determined by ELISPOT or single cell sequencing. Results Our results have confirmed reactivity of previously known Coccidioides antigens while also identifying new antigens not previously associated with T cell immunogenicity. T cell responses varied between animals and humans, but similar antigens were recognized. Th17 and Th1 immune responses and responding clones were identified by single cells sequencing. Conclusion Similar responses were seen in PTM and humans, supporting the PTM model for VF research. Some identified T cell clones recognized antigens that have been associated with a mouse protective DNA vaccination. These antigens and their related clones will be tracked in challenged or vaccinated PTM to aid in the identification of correlates of protection. Finally, the reactive antigens and their epitopes can be further investigated for potential diagnostic tools or vaccines. Funding Source U19AI166058, 3U19AI166058-02S1, P51OD010425, U42OD011123 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)
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