RARE DISEASE
Coccidioidomycosis
Coccidioidomycosis
Coccidioidomycosis
Synonyms: California disease, Coccidioides infection, Desert fever, Desert rheumatism, San Joaquin valley fever, Valley fever
Synonyms: California disease, Coccidioides infection, Desert fever, Desert rheumatism, San Joaquin valley fever, Valley fever
Synonyms: California disease, Coccidioides infection, Desert fever, Desert rheumatism, San Joaquin valley fever, Valley fever
Drug discovery
8
drugs
With orphan designations
Overview
Coccidioidomycosis (Valley fever) is a fungal infection caused by Coccidioides immitis and C. posadasii, primarily contracted through inhalation of arthroconidia in endemic arid regions of the southwestern US, Mexico, and Central/South America. Approximately 40% of cases develop respiratory symptoms (cough, fatigue, fever), while 5-10% progress to chronic pulmonary or disseminated disease, particularly affecting immunocompromised individuals. Diagnosis relies on serologic testing (IgM/IgG), with treatment guided by disease severity and host factors [1][6][13][16].
Key Clinical Information
Burden
Annual US incidence: 10,000-20,000 reported cases (2019 peak: 20,061), with significant underdiagnosis [4][7][9]
Hospitalization rate: 8-56% in disseminated cases; mortality 5-70% in immunocompromised patients [4][7][14]
Economic impact: $50M/year in hospitalization costs; prolonged therapy (months-years) increases treatment burden [4][14][18]
Therapies
Mild/self-limited: Observation (40% resolve without treatment) [1][18]
Moderate-severe: Fluconazole (400-1,200 mg/day) or itraconazole (200 mg BID) for 3-6 months [3][8][13]
Disseminated/meningitis: Amphotericin B (0.7-1 mg/kg/day) initially, transitioning to azoles; lifelong suppression often required for CNS involvement [8][13][19]
Categories: rare infectious diseases
Research Papers
901 drug discovery papers about Coccidioidomycosis, with 11 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
901 drug discovery papers about Coccidioidomycosis, with 11 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2026-06-09 | In silico identification and validation of vaccine and drug targets in Coccidioides posadasii through integrated genomic, proteomic, and molecular modeling approaches.
Coccidioides posadasii is a pathogenic fungus endemic to the arid regions of the Americas, causing coccidioidomycosis, a debilitating respiratory infection. Coccidioides infection is caused by breathing arthroconidia generated by mycelia that grow in desert soil. Arthroconidia develop inside the lung into massive, multinucleated spherules that are pathognomonic. Despite its significant impact on public health, there remains a paucity of research investigating novel therapeutic approaches to combat this disease. Addressing this research gap, our study employs a multi-faceted approach integrating genomics, proteomics, and computational biology to elucidate the pathogenesis of C posadasii and identify potential therapeutic targets. Our methodology involved retrieving genomic data from 5 strains of C posadasii and generating core proteomes using OrthoFinder, enabling the identification of extracellular proteins as vaccine candidates and metabolic pathways as drug targets. This approach benefits the research study by providing a comprehensive understanding of the molecular mechanisms underlying C posadasii infection, thereby facilitating the development of targeted interventions against valley fever. Our results reveal promising drug-like candidates for drug targets and vaccine targets CID:123631, CID:193962, CID:3045233, CID:6741, CID:214348, CID:11450633 with the identified proteins demonstrating potential efficacy against C posadasii. As we embark on the journey towards translating these discoveries into clinical practice, our findings offer hope for a future where effective treatments for coccidioidomycosis are within reach, promising relief to countless individuals afflicted by this devastating disease.
2026-05-22 | DECTIN-1 stalk length determines binding ability, immune response, and survival in a mouse model of coccidioidomycosis.
Coccidioidomycosis is a leading cause of pneumonia in the endemic area of the Sonora desert and the central valley of California. The causative agent are the fungi Coccidioides immitis and C. posadasii. While most infections ultimately resolve without treatment, some infections spread to the periphery and cause serious and even fatal illness. Much work has shown that a T cell response with production of interleukin-17A and interferon ɣ is critical. Less work has focused on innate responses that ultimately set the stage for the adaptive response. Genetic analysis in both mice and man have shown an important role for DECTIN-1. DECTIN-1 is a C-type lectin receptor that recognizes β-glucans, the main cell wall component of many fungi. Initial recognition through DECTIN-1 modulates fungal binding, host cell uptake, and induces production of a number of cytokines and chemokines. C57BL/6 mice carry a point mutation altering splicing of exon 3, leading to a shorter DECTIN-1 protein lacking a portion of the extracellular stalk. We created mutant C57BL/6 mice to allowing expression of a long-stalk DECTIN-1 consistent with other mouse strains and humans. We directly examined the role of DECTIN-1 stalk length on resistance to infection with the β-glucan-dominant pathogen, C. posadasii. C57BL/6 mice expressing long-stalk DECTIN-1 bound more β-glucan per cell, produced more cytokines, and decreased mortality and dissemination after Coccidioides infection compared with wild-type littermates. The length of the DECTIN-1 stalk controls the outcome of Coccidiodes infection by differential binding and early production of protective cytokines.
2026-02-25 | Use of Epoetin Alfa for Anemia of Chronic Disease in a Jehovah's Witness Teenager With Disseminated Coccidioidomycosis: A Case Report.
Anemia of chronic disease is a common complication of prolonged infection and systemic inflammation and can be difficult to manage in patients who decline blood transfusion, such as Jehovah's Witnesses. Erythropoiesis-stimulating agents are widely used in renal and oncologic settings but are rarely reported in infection-associated anemia among pediatric or young adult patients. We describe a 19-year-old Jehovah's Witness male with disseminated Coccidioides immitis infection complicated by severe anemia of chronic disease. Because blood transfusion was declined, epoetin alfa was administered as a transfusion-sparing strategy prior to surgical intervention. This case highlights a potential role of epoetin alfa as an alternative strategy for managing infection-related anemia in select patients when transfusion is not an option.
2025-09-26 | The Use of Genetics and Immunology in the Diagnosis and Care of Advanced Coccidioidomycosis: Where Are We Going?
Coccidioidomycosis (CM) is an endemic disease in the western United States, northern Mexico, and Central and South America. The severity of coccidioidal infection is highly variable, with potential factors including comorbidities and the patient's innate and adaptive immune response. Based on data from a predominantly healthy and mainly Caucasian male survey conducted nearly a century ago, approximately 60% of infections are asymptomatic, with an estimated 40% of people experiencing some respiratory symptoms; with 10% of those diagnosed with CM. Disseminated disease occurs in approximately 1% of cases and can involve the meninges and, potentially, any place in the body. It is not yet fully understood why some people experience severe disease while many people do not; it is understood that the immune response has a major role. Immunomodulators, including dupilumab and interferon-gamma (IFN-γ), have shown promise in treating patients with disseminated infection. This article summarizes the latest genetic and immunologic evidence demonstrating immune dysfunction. Immunomodulators and potential therapeutic strategies based on the above are reviewed.
2025-05-29 | Interferon-γ Therapy in Patients With Refractory Disseminated Coccidioidomycosis.
Refractory disseminated coccidioidomycosis (DCM) is a severe disease with limited treatment options. This report reviews our own and prior published experiences using adjunctive interferon-γ therapy in refractory DCM, showing overall favorable responses in patients without signal transducer and activator of transcription 1 gain-of-function mutations.
antibodies
2026-09-07 | Coccidioidomycosis in Patients Treated with Dupilumab: A Descriptive Case Series.
A Th2-favored phenotype can predispose individuals to symptomatic and disseminated coccidioidomycosis. Dupilumab, which impedes Th2 immunity, is sometimes used adjunctively for disseminated coccidioidomycosis. To determine whether dupilumab alters the clinical course of coccidioidomycosis, we retrospectively reviewed records of 1,561 patients who received dupilumab; 42 had coccidioidomycosis diagnosed from October 6, 2018, through July 16, 2025 (Mayo Clinic [Phoenix, Arizona]). Eleven patients received dupilumab before having symptomatic coccidioidomycosis, and 3 received dupilumab before asymptomatic coccidioidomycosis was identified. Twenty-eight patients received dupilumab after coccidioidomycosis was diagnosed: 16 were asymptomatic and seropositive, without reactivation on dupilumab, and 12 had ongoing symptoms (most eventually resolved). No patients had adjunctive dupilumab treatment. Three patients had disseminated coccidioidomycosis: 2 initiated dupilumab after coccidioidomycosis was diagnosed and 1 before, and each eventually had symptomatic improvement. We did not observe patterns of coccidioidomycosis worsening after dupilumab initiation or an increased prevalence of coccidioidomycosis among patients already receiving dupilumab.
2026-07-10 | Genetic and transcriptomic determinants of disseminated coccidioidomycosis identify a founder variant in NLRX1 and ancestry-specific rare variants in immune response genes.
Coccidioidomycosis, also known as Valley Fever, is a fungal disease endemic to the Americas that kills hundreds annually, yet the host factors that lead to increased risk of life-threatening dissemination of coccidioidomycosis remain poorly understood. We assembled the largest comprehensively sequenced coccidioidomycosis cohort to date, comprising 795 individuals with laboratory confirmed coccidioidomycosis and clinical disease severity phenotyping, many with paired whole blood genomic and transcriptomic data. Individuals with greater than 50% African genetic ancestry have increased risk for disseminated coccidioidomycosis (DCM) cases (OR=13.37, p=1.08×10-18), reflecting ancestry-associated differences in allele frequencies at immune loci. Transcriptomic profiling (n=267) revealed upregulation of interferon-inducible genes IFI44 and IFI44L, the fungal recognition receptor CLEC4D, and pro-inflammatory protein S100A12, with sex-specific expression differences in immune cell composition. Gene-burden testing identified NOD-like receptor NLRX1 as the only gene carrying significantly more damaging rare variants than expected by chance (p=5.85×10-4). We identified a rare missense variant, NLRX1 p.Arg252Trp (rs145644388), in five patients with DCM that represents a founder variant: all carriers share African local genetic ancestry and carry 0.6-1.1 centimorgans of identical-by-descent sequence, indicating origin from a common ancestor. In gnomAD, NLRX1 p.Arg252Trp shows has higher allele frequency in African (AF=0.00615) compared to European (AF= 2.25×10-5) populations, directly linking this rare variant to population-level African genetic ancestry enrichment in DCM. NLRX1 disruption impairs LC3-associated phagocytosis, an antifungal mechanism in macrophages. Together, these findings reveal both immune gene expression dysregulation and rare-variant architectures associated with African genetic ancestry underlying severe coccidioidomycosis and identify new targets for risk stratification and treatment.
2026-02-12 | Exhausted T cell phenotypes in disseminated coccidioidomycosis.
Coccidioidomycosis presents clinically as a spectrum ranging from self-limiting Uncomplicated Valley Fever (UVF) in most cases to life-threatening Disseminated Coccidioidomycosis (DCM) in rare individuals. A few patterns of immunologic deficits allowing for dissemination have been identified, though the specific defects in most individuals with DCM remain undefined. We hypothesized that chronic antigen exposure in DCM engenders a state of T cell exhaustion. From a cohort of over 300 subjects with confirmed diagnoses of coccidioidomycosis, circulating T cell phenotypes were characterized via flow cytometry and Coccidioides-specific T cell responses were measured using the Activation-Induced Marker (AIM) assay. Male sex was significantly associated with disseminated disease (odds ratio 2.5; 95% CI: 1.5 - 4.0). 52% of subjects showed Coccidioides-specific T cell responses in our AIM assay. We noted a significant difference in subjects sampled in the first year of diagnosis, where only 8% of DCM subjects had T cell responses during this time, as compared to 44% of UVF subjects (p = 0.04). Among DCM patients with detectable AIM responses, CD4+ T cells demonstrated an exhausted phenotype with elevated PD-1 expression compared to UVF subjects. In vitro PD-1 blockade augmented IFNγ production in most tested DCM subjects. These findings suggest that dissemination may occur in some individuals during a period of impaired antigen-specific T-cell activity. Importantly, these responses can be augmented in vitro by PD-1 blocking antibodies, supporting further study of immune checkpoint therapy as an adjunct to antifungal treatment in disseminated coccidioidomycosis.
2025-10-03 | Type-2 immune skewing in patients with disseminated coccidioidomycosis.
Disseminated coccidioidomycosis (DCM) is an often fatal and otherwise intractable condition requiring lifelong antifungal treatment. We have previously shown that a deranged polarization of CD4+ T cells toward a Type-2 phenotype can exist in the context of DCM. Here we studied a large population of subjects to determine the frequency of abnormal Type-2 skewing of CD4+ T cells in patients with coccidioidomycosis and to identify underlying genetic mechanisms supporting this skew. We collected peripheral blood mononuclear cells from 204 patients with coccidioidomycosis, including 96 patients with disseminated disease. We measured immune phenotypes and cytokine production by CD4+ T cells from patients and healthy controls, and comparisons between groups were made based on disease severity and demographics. Whole genome sequencing was conducted on 149 individuals who also had cytokine profiling. We found that ~20% of DCM patients had a CD4+ T-cell compartment that was abnormally skewed toward a Type-2 (IFN-γ-IL-4+) phenotype. Type-2 skewing was highly correlated with male sex, with 80% of moderately skewed (Th2:Th1 ratio > 1.5) and 100% of severely skewed (Th2:Th1 ratio > 2) patients being male. Co-culture of T cells with the IL4R/IL13R-blocking antibody dupilumab rectified their Th1/Th2 skewing. Sequencing revealed rare variants in genes involved in the IL-12-IFN-γ axis in several Type-2 skewed patients, and we validated one such variant in IFNGR1 as hypomorphic. Patients with DCM, especially those who are male, should be screened for Type-2 skewing of CD4+ T cells. Patients with Type-2 skewing should be additionally screened for genetic defects in the IL-12-IFN-γ axis. Our findings give a mechanistic rationale for exploring blockade of IL4R as a treatment option in Type-2 skewed patients with refractory coccidioidomycosis.
2025-04-25 | Immunomodulation in the Treatment of Disseminated Coccidioidomycosis
Introduction Coccidioidomycosis, commonly known as Valley fever, is an endemic fungal infection with a growing impact in the western United States. Patients with disseminated coccidioidomycosis (DCM) represent a rare and life-threatening subset of Valley fever who face years or a lifetime of antifungals to manage their disease. Immunocompromised patients with defective type 1 immunity or excessive type 2 immunity have an increased risk of dissemination. We previously published a single case employing the IL4/IL13 blocker dupilumab as an adjuvant to antifungal therapy. Here we present ten cases of patients in which adjuvant immunomodulation was provided for severe coccidioidomycosis. Methods This is not an interventional trial. Cases were identified at UCLA by infectious disease experts in conjunction with immunology, and all subjects were deemed to be maximally treated with multiple conventional antifungals. Informed consent was obtained. We performed intracellular cytokine staining on CD4+ T cells and measured proportions of interferon gamma (IFN-γ), IL-4, and IL-17A–producing T cells. Treatment with IFN-γ was offered to those subjects showing life-threatening progression of disease despite maximal conventional care. Treatment with dupilumab was offered to those with excessive type-2 skewing. Clinical outcomes were assessed by laboratory studies, imaging results, and mycosis score. Results Our data follow 10 subjects for a median of 6 months after treatment. Our subjects showed excessive type 2-to-1 ratios, mostly due to excessive type 2 immune skewing and less often in subjects with poor type 1 responses. We found reduction of polyclonal type 2 responses in response to treatment with dupilumab. Clinical outcomes in all ten subjects were improved above the baseline state. Conclusions Our work offers a new treatment employing immune modulation by cytokine blockade to treat a life-threatening infectious disease. Patients with poorly controlled disease may benefit from IFN-γ. Furthermore, subjects exhibiting a Th2-skewed response may benefit from dupilumab. Following the Casadevall damage–response framework, this tailored approach aligns immunomodulation with the underlying immunopathology. These observations provide evidence to support proper clinical trials of IFN-γ and dupilumab. Further research is needed to better characterize why cocci disseminates in certain subjects and which patients will benefit from immunomodulation.
small molecules
2026-09-25 | Accelerating research to keep pace with the rising incidence of coccidioidomycosis.
The number of infections caused by the fungal pathogen Coccidioides is rising. In tandem, the number and breadth of researchers studying this important dimorphic fungal pathogen are growing as well. This review focuses on recent advances in the field and identifies areas primed for ongoing rapid growth, with the goal to improve treatments for coccidioidomycosis as soon as reasonably possible. These areas include building genetic tools, high-throughput drug screening, developing immunomodulatory therapies for coccidioidomycosis, and incorporating research methodologies that can be performed outside of the biosafety level 3 laboratory.
2026-07-20 | Olorofim in Treatment of Patients With Poorly Controlled Disseminated Coccidioidomycosis : A Single-Group, Open-Label, Phase 2b, Multicenter Study.
Olorofim, a novel dihydroorotate dehydrogenase inhibitor, may be efficacious in patients with disseminated coccidioidomycosis (DCM) who lack alternative treatment options. To evaluate olorofim effectiveness and adverse events in patients with DCM. Single-group, open-label, phase 2b study. (ClinicalTrials.gov: NCT03583164). Ten U.S. sites. Forty-one patients with DCM and limited or no treatment options. Patients received olorofim alone or in combination with ongoing standard of care during an 84-day main treatment phase. Extended treatment was offered to patients. Mycoses Study Group-European Organization for Research and Treatment of Cancer (MSG-EORTC) criteria for global response based on subcategories of clinical, radiologic, and mycologic response were adjudicated by an independent data review committee (DRC) at days 42 and 84 (main treatment phase). Because the slow pace of serologic improvement in DCM limits global response to stable at best, this article focuses on patient clinical responses. Treatment-emergent adverse events (TEAEs) were compiled for both treatment phases. Forty-one patients with DCM were enrolled from May 2019 to August 2022. Thirty-nine (95.1%) did not have immunosuppression. Central nervous system disease was present in 30 (73.2%) patients, and 13 (43.3%) had a ventriculoperitoneal shunt with or without an Ommaya reservoir. Clinical success as adjudicated by the DRC occurred in 31 of 41 patients (75.6% [95% CI, 59.7% to 87.6%]) at day 42 and 30 of 41 patients (73.2% [CI, 57.1% to 85.8%]) at day 84. The main TEAE was hepatic biochemistry elevation in 9 of 41 patients (21.9%), which was managed by liver enzyme monitoring and dose reduction or pause in 8 patients (19.5%) and drug discontinuation in 1 patient (2.4%). This was a single-group, open-label trial, but a randomized controlled trial would be preferable. Olorofim showed effectiveness in patients with DCM with limited or no therapeutic options. F2G, Ltd.
2026-07-16 | Persenone A from Avocados Exhibits Potent Anti-Fungal Activity against Coccidioides.
Coccidioidomycosis, or Valley fever, is a fungal respiratory disease caused by Coccidioides immitis or Coccidioides posadasii. Clinical manifestations range from asymptomatic infection to chronic pulmonary disease. Despite the increasing endemic range and affected population, therapeutic strategies display moderate efficacy and adverse side effects. This study explores California's rich botanical diversity as a source for agents that inhibit the early stages of Coccidioides development. We established a screening protocol containing a colorimetric metabolism assay and microscopic imaging. We then applied this protocol to extracts derived from local plants in San Diego, California, and discovered a potent inhibitor, persenone A, from avocados.
2026-06-22 | Severe Pulmonary Coccidioidomycosis Treated With Systemic Corticosteroids in an Adolescent Child.
Coccidioidomycosis (CM) is an emerging public health challenge due to an increasing number of cases in the U.S. Diagnosis may be challenging because of its nonspecific presentation, which may lead to treatment delays. In addition, the optimal management of severe pulmonary CM remains unclear. We present the case of an 18-year-old immunocompromised renal transplant recipient with a history of systemic lupus erythematosus who developed acute respiratory distress syndrome (ARDS) secondary to severe pulmonary CM. Following initiation of systemic corticosteroids treatment with standard-of-care antifungals, she demonstrated improved clinical response. Severe pulmonary CM may lead to a significant multiorgan inflammatory response in this infection. Our case explores corticosteroid treatment to downregulate this pathophysiologic process and help facilitate clinical resolution of the critical respiratory symptoms and limit morbidity associated with this infection.
2026-05-28 | Myeloid-derived suppressor cell (MDSC)-like neutrophils induced by pulmonary infection with Coccidioides posadasii exacerbate disease by suppressing CD4+ T cell immunity.
Coccidioidomycosis is a pulmonary disease caused by the dimorphic fungus Coccidioides, which is endemic to the southwestern United States and South America. Coccidioides grows as septate hyphae in soil and forms spores that can become airborne during mechanical disruption of the soil. In the lungs, the inhaled spores develop into large multinucleated spherules, a unique morphology among medically important Coccidioides species, and reproduce by endosporulation. A hallmark of the host immune response toward endosporulating spherules is the robust recruitment and infiltration of Ly6G+ neutrophils. However, the effectiveness of Ly6G+ neutrophils against Coccidioides remains to be studied. Myeloid-derived suppressor cells (MDSCs) are immunosuppressive and share an origin and many phenotypic features with neutrophils. Here, we demonstrated that Ly6G+ cells, but not Ly6C+ cells, increased lung expression of the inhibitory programmed death-ligand 1 (PD-L1) in diseased mice. The Ly6G+PD-L1+ cells share common characteristics of granulocytic MDSCs. Bone-marrow-derived GR-1+ myeloid cells, including both Ly6G+ and Ly6C+ cells, suppressed the proliferation of CD4+ T cells after exposure to spherules. Furthermore, isolated GR-1+ cells from the lungs and spleens of Coccidioides-infected non-protected mice also suppressed CD4+ T cell proliferation, thereby diminishing adaptive T cell responses. Adoptive transfer of GR-1+ myeloid cells isolated from the lungs of Coccidioides-infected mice, or derived from bone marrow exposed to paraformaldehyde-killed spherules, into vaccine-protected recipients exacerbated coccidioidomycosis through the reduction of protective Th1 and Th17 responses. Altogether, we demonstrate that pulmonary infiltration of MDSC-like neutrophils, in non-vaccinated mice, play a detrimental role in coccidioidomycosis by inhibiting protective CD4+ T cell responses. Dimorphic fungi are primary pathogens that infect both immunocompetent and immunocompromised hosts. Fungal pathogens have evolved sophisticated strategies to evade innate immune responses, which have not been well studied. Recently, myeloid-derived suppressor cells (MDSCs) have been described in the pathogenesis of several fungal infections, including Candida albicans and Cryptococcus neoformans. Here, we use a live-attenuated vaccine model to investigate the role of Ly6G+ myeloid cells during Coccidioides infection in mice. We have shown that pulmonary Coccidioides posadasii infection leads to the accumulation of programmed death-ligand 1 (PD-L1)+Ly6G+ MDSC-like neutrophils that suppress CD4+ T cell proliferation and exacerbate disease by reducing protective Th1 and Th17 responses. Moreover, adoptive transfer of GR-1+ myeloid cells isolated from Coccidioides-infected mice into vaccine-protected recipient mice reduced protective efficacy by increasing fungal burden and disease severity. Our data suggest that immunosuppressive Ly6G+PD-L1+ MDSC-like neutrophils play a detrimental role by suppressing protective T cell responses in pulmonary Coccidioides infection.
vaccines
2026-06-25 | Intent to Accept a Valley Fever Vaccine for Humans and Dogs and Factors Influencing Intended Uptake: A Cross-Sectional Survey in Two Endemic Regions.
As Valley fever (coccidioidomycosis) vaccine candidates progress towards human trials, a challenge to their eventual introduction is understanding vaccine demand and addressing vaccine hesitancy. We assessed intent to accept a Valley fever vaccine for humans and dogs in two populations living in highly endemic regions: employees at Kern Medical (KM) in Bakersfield, California (N = 103) and members of the public in West Texas (N = 230). We compared the weighted proportions of each population willing to vaccinate themselves and their dogs by demographic and coccidioidomycosis risk factors and assessed the importance of vaccine-related factors on vaccine uptake in each population. We found that 42% (95% confidence interval (CI): 34-49%) of West Texas residents and 76% (95% CI: 63-85%) of KM employees were willing to accept a coccidioidal vaccine, while 49% (95% CI: 41-58%) of West Texas residents and 74% (95% CI: 58-86%) of KM employees were willing to vaccinate their dogs. Among West Texas residents, vaccination willingness was significantly higher among those with prior awareness of Valley fever (adjusted odds ratio (aOR): 3.83, 95% CI: 1.73, 8.49). Across both study populations, absence of side effects was the most important condition that would increase vaccination willingness. Our results indicate substantial interest in a Valley fever vaccine while suggesting that increased Valley fever awareness and minimal vaccine side effects may be important for increased uptake.
2025-11-17 | Fungal vaccines: so needed, so feasible, and yet so far off.
Invasive fungal infections carry high morbidity and mortality, but there are no fungal vaccines. In this issue of the JCI, Okaa et al. report that endonuclease 2 (Eng2), an antigen shared by the Blastomyces, Histoplasma, and Coccidioides species of fungi, elicits protective immunity in mice against blastomycosis, histoplasmosis, and coccidioidomycosis. These results establish a common antigen that can elicit protection against multiple mycoses, encouraging the development of a pan-fungal vaccine. The road to fungal vaccines is made difficult by the need for effectiveness in immunocompromised individuals, the sporadic nature of fungal disease, and the economics of vaccine development. Despite these hurdles, there is optimism that such vaccines can be developed and perhaps find usefulness as adjuncts to antifungal therapy.
2025-10-08 | Endoglucanase 2 (Eng2), a shared immunodominant antigen in dimorphic fungi that elicits immunity during infection.
We describe here a shared surface and cell wall protein, endoglucanase 2 (Eng2), expressed on the etiological agents that cause the endemic systemic mycoses of North America - Blastomyces, Coccidioides, and Histoplasma. We demonstrate that, despite sequence variation of the protein across these related fungi, exposure to Eng2 vaccinated and protected inbred and humanized HLA-DR4 strains of mice against lethal experimental infections with these fungi by eliciting adaptive immunity mediated by CD4+ T cells. We also show that CD4+ T cell precursors against Eng2 were detectable in naive individuals and that patients who had recovered from these infections evinced a memory and recall CD4+ T cell response to Eng2 and its immunodominant epitopes that we have mapped. We created and cataloged new tools and information, such as immunodominant peptide epitopes of Eng2 from each fungus recognized by inbred mice and humans, and we engineered peptide-MHC II tetramers to track T cells in inbred and HLA-DR4-humanized mice. These tools and tetramers will be useful for those who study these infections in mice and humans. Last, because most patients demonstrated immune memory and recall responses against Eng2, our work offers tools for the diagnosis of this collection of infectious diseases across North America.
2025-06-05 | Recall interferon-γ responses against Coccidioides are a surrogate marker for vaccine response in dogs.
To develop an interferon γ (IFN-γ) recall assay to detect a T-cell response following vaccination because antibody is seldom detected in Δcps1-vaccinated dogs. Peripheral blood mononuclear cells were collected from naturally infected dogs with a history of coccidioidomycosis or dogs from a nonendemic area. Two- to 5-month-old Beagles were vaccinated 2 to 4 times up to 28 days apart with live, avirulent Δcps1 and bled on study days 42, 68, or 90. Peripheral blood mononuclear cells were stimulated with Δcps1 and stained to detect CD4+ T-cell IFN-γ expression. The percentage of CD4+IFN-γ+ T cells compared to unstimulated baseline was calculated for each dog. All 5 naturally infected dogs with coccidioidomycosis had T-cell IFN-γ responses, and the 2 unexposed nonendemic dogs did not. Fourteen of 15 dogs vaccinated with Δcps1 had recall IFN-γ responses. Subcutaneously vaccinated dogs (n = 5) had a mean 1.85-fold increase in IFN-γ over baseline, whereas IM-vaccinated dogs (n = 10) were a mean of 6- to 10-fold higher. The percentage of CD4+IFN-γ+ cells was higher from restimulated cells compared to baseline in both SC- and IM-vaccinated dogs (SC twice [n = 5]: 95% CI, 0.001 to 0.543; IM twice [n = 5]: 95% CI, 0.9734 to 1.948; IM 4 times [n = 5]: 95% CI, 1.207 to 5.083). The T-cell IFN-γ recall assay of peripheral blood mononuclear cells from vaccinated dogs detects a cell-mediated immune response to the Δcps1 vaccine. This assay has potential utility as a surrogate marker for vaccine-induced immunity.
2024-10-04 | From soil to clinic: current advances in understanding Coccidioides and coccidioidomycosis.
SUMMARYCoccidioides immitis and Coccidioides posadasii are fungal pathogens that cause systemic mycoses and are prevalent in arid regions in the Americas. While C. immitis mainly occurs in California and Washington, C. posadasii is widely distributed across North and South America. Both species induce coccidioidomycosis (San Joaquin Valley fever or, more commonly, Valley fever), with reported cases surging in the United States, notably in California and Arizona. Moreover, cases in Argentina, Brazil, and Mexico are on the rise. Climate change and environmental alterations conducive to Coccidioides spp. proliferation have been recently explored. Diagnostic challenges contribute to delayed treatment initiation, compounded by limited therapeutic options. Although antifungal drugs are often effective treatments, some patients do not respond to current therapies, underscoring the urgent need for a vaccine, particularly for vulnerable populations over 60 years old relocating to endemic areas. Despite recent progress, gaps persist in the understanding of Coccidioides ecology, host immune responses, and vaccine development. This review synthesizes recent research advancements in Coccidioides ecology, genomics, and immune responses, emphasizing ongoing efforts to develop a human vaccine.
other
2026-03-27 | Immune-Based Prevention and Therapy Against Coccidioidomycosis: Current and Emerging Approaches.
Coccidioidomycosis (CM) is a fungal infection caused by the inhalation of airborne arthroconidia released by Coccidioides spp. Endemic areas include the southwestern United States, Mexico, and parts of South America. The estimated CM cases exceed 300,000 per year. Current treatment for CM is limited and primarily relies on antifungals such as azoles and Amphotericin B. Moreover, concerns about drug cytotoxicity and rising of azole-resistance underscore the need for alternative or adjunctive immune-based prevention and therapies. This review presents recent advances in immune CM intervention and discusses the potential application of emerging antifungal immunotherapy to treat invasive CM. For preventive vaccination, we reviewed the recent development of subunit protein vaccines and mRNA-based vaccines. Prospects for formulating vaccines with potent adjuvants and delivery systems to enhance protective immunity against CM are also provided. For immunotherapy, we reviewed recent reports of antifungal treatment with immunomodulators, CAR-cells and checkpoint inhibitors. Finally, we discuss the application of experimental animal and in vitro models for advancing vaccine and immunotherapeutic development for CM.
2023-08-21 | Application of anti-fungal vaccines as a tool against emerging anti-fungal resistance
After viruses and bacteria, fungal infections remain a serious threat to the survival and well-being of society. The continuous emergence of resistance against commonly used anti-fungal drugs is a serious concern. The eukaryotic nature of fungal cells makes the identification of novel anti-fungal agents slow and difficult. Increasing global temperature and a humid environment conducive to fungal growth may lead to a fungal endemic or a pandemic. The continuous increase in the population of immunocompromised individuals and falling immunity forced pharmaceutical companies to look for alternative strategies for better managing the global fungal burden. Prevention of infectious diseases by vaccines can be the right choice. Recent success and safe application of mRNA-based vaccines can play a crucial role in our quest to overcome anti-fungal resistance. Expressing fungal cell surface proteins in human subjects using mRNA technology may be sufficient to raise immune response to protect against future fungal infection. The success of mRNA-based anti-fungal vaccines will heavily depend on the identification of fungal surface proteins which are highly immunogenic and have no or least side effects in human subjects. The present review discusses why it is essential to look for anti-fungal vaccines and how vaccines, in general, and mRNA-based vaccines, in particular, can be the right choice in tackling the problem of rising anti-fungal resistance.
2019-12-26 | [Dialyzed leukocyte extracts for the treatment of recurrent and severe infections in pediatric patients with cellular immunodeficiency: 15 years of experience].
Dialyzable leukocyte extracts (DLE) have been used to treat several cellular immunodeficiency. To review the experience of a tertiary hospital in the use of DLE for the treatment of recurrent or severe infections in children with acquired cellular immunodeficiency not due to HIV. We reviewed the medical records of all children who received treatment with EDL of human or bovine origin between 1986 and 2000 to detect recurrent or severe infections without response to a specific antimicrobial therapy and with a quantitative or qualitative deficit in the cellular immune response. The dose of DLE was adjusted according to the percentage of T lymphocytes; the evolution of the patient was evaluated retrospectively for 5 years, the immune response was evaluated by subpopulation of lymphocytes and intradermal tests and inhibition of the leukocyte migration assay (LIF) to PPD, coccidioidin, varidase and candidin. 150 children received DLE, age 7.0 ± 5.9 years. The most frequent indications included upper respiratory tract (71%), lower respiratory tract (43%), gastrointestinal tract (15%), urinary tract (15%) and neurological infections (4%) and coccidioidomycosis (3%). After starting the DLE, the numbers of T lymphocytes, LIF to PPD and varidase (> 20%) and the intradermal induration of the test increased (p <0.001). In 6 patients (4%) recurrences of respiratory and gastrointestinal tract infections were observed, which resolved, no adverse effects attributable to the DLE were reported. The use of DLE for recurrent or severe infectious processes in children with cellular immune deficit improved the clinical evolution and the immunological parameters evaluated without adverse effects attributable to their use. Antecedentes: Los extractos dializados de leucocitos (EDL) han sido utilizados en el tratamiento de diversos defectos de la inmunidad celular. Objetivo: Revisar la experiencia en el uso de EDL para tratar infecciones recurrentes o severas en niños con inmunodeficiencia celular adquirida no debida a virus de la inmunodeficiencia oportuna. Métodos: Se revisaron expedientes de niños tratados con EDL humano o bovino entre 1986 y 2000, por infecciones recurrentes o severas sin respuesta a antimicrobianos y con déficit en la respuesta inmune celular. La dosis se ajustó por el porcentaje de poblaciones de linfocitos T. En el seguimiento a cinco años, la respuesta inmune se evaluó por subpoblaciones de linfocitos, intradermorreacción e inhibición de la migración de leucocitos (LIF) a PPD, coccidioidina, varidasa y candidina. Resultados: 150 niños recibieron EDL, edad 7.0 ± 5.9 años. Las indicaciones más frecuentes incluyeron infección respiratoria superior (71 %), respiratoria inferior (43 %), gastrointestinal (15 %), urinaria (15 %), neuroinfección (4 %) y coccidioidomicosis (3 %). Se incrementaron los linfocitos T, el LIF a PPD y varidasa (> 20 %), así como la induración en pruebas de intradermorreacción (p < 0.001). Se resolvieron las infecciones que se presentaron (4 %). No se reportaron efectos adversos. Conclusiones: El uso de EDL mejoró los parámetros inmunológicos y la evolución clínica en niños con déficit inmune celular.
2019-02-20 | Dendritic cell-based immunization induces Coccidioides Ag2/PRA-specific immune response
Valley Fever, or coccidioidomycosis, is caused by a soil-borne, highly virulent fungal pathogen, Coccidioides spp. Infection with Coccidioides can be life-threatening. Since an effective treatment is not available and the T cell-mediated immune response is protective, vaccine development is of interest. In this study, a primary dendritic cell (DC)-vaccine was evaluated for its ability to stimulate Coccidioides antigen-specific immune response in an extremely susceptible BALB/c mouse model. The DC-vaccine (Ag2-DC) was prepared by non-virally transfecting the primary bone marrow-derived DCs with a plasmid DNA encoding Ag2/PRA (protective epitope of Coccidioides). Mice were intranasally immunized with Ag2-DC on days 2 and 10. Immunized mice were necropsied on days 8, 32, and 44. Major organs and blood samples were harvested. The most common indicators of injury (protein, lactate, and albumin), Ag/PRA-specific cytokine-secreting cells, and IgG and its isotypes were determined by biochemical and immunologic assays, respectively. No signs of sickness were noted. Similarly, no significant changes were observed in the levels of total lung protein, lactate, and albumin, in immunized mice compared with healthy control mice. Interferon (IFN-γ), and interleukin (IL)-4 and IL-17 cytokine-secreting cells were observed in lung and lymph nodes upon Ag2-DC immunization. Our results showed that the levels of serum IgG and its isotypes were increased in Ag2-DC-immunized mice. This report provides evidence of DC immunization-stimulated Ag2/PRA-specific immune responses.
2018-05-21 | Helper T‐cell responses and pulmonary fungal infections
Summary The mucosal surface of the respiratory tract encounters microbes, such as fungal particles, with every inhaled breath. When pathogenic fungi breach the physical barrier and innate immune system within the lung to establish an infection, adaptive immunity is engaged, often in the form of helper CD4 T‐cell responses. Type 1 responses, characterized by interferon‐ γ production from CD4 cells, promote clearance of Histoplasma capsulatum and Cryptococcus neoformans infection. Likewise, interleukin‐17A (IL‐17A) production from Th17 cells promotes immunity to Blastomyces dermatitidis and Coccidioides species infection by recruiting neutrophils. In contrast the development of T helper type 2 responses, characterized by IL‐5 production from T cells and eosinophil influx into the lungs, drives allergic bronchopulmonary aspergillosis and poor outcomes during C. neoformans infection. Experimental vaccines against several endemic mycoses, including Histoplasma capsulatum , Coccidioides , Cryptococcus and Blastomyces dermatitidis , induce protective T‐cell responses and foreshadow the development of vaccines against pulmonary fungal infections for use in humans. Additionally, recent work using antifungal T cells as immunotherapy to protect immune‐compromised patients from opportunist fungal infections also shows great promise. This review covers the role of T‐cell responses in driving protection and pathology in response to pulmonary fungal infections, and highlights promising therapeutic applications of antifungal T cells.
proteins
2026-06-09 | In silico identification and validation of vaccine and drug targets in Coccidioides posadasii through integrated genomic, proteomic, and molecular modeling approaches.
Coccidioides posadasii is a pathogenic fungus endemic to the arid regions of the Americas, causing coccidioidomycosis, a debilitating respiratory infection. Coccidioides infection is caused by breathing arthroconidia generated by mycelia that grow in desert soil. Arthroconidia develop inside the lung into massive, multinucleated spherules that are pathognomonic. Despite its significant impact on public health, there remains a paucity of research investigating novel therapeutic approaches to combat this disease. Addressing this research gap, our study employs a multi-faceted approach integrating genomics, proteomics, and computational biology to elucidate the pathogenesis of C posadasii and identify potential therapeutic targets. Our methodology involved retrieving genomic data from 5 strains of C posadasii and generating core proteomes using OrthoFinder, enabling the identification of extracellular proteins as vaccine candidates and metabolic pathways as drug targets. This approach benefits the research study by providing a comprehensive understanding of the molecular mechanisms underlying C posadasii infection, thereby facilitating the development of targeted interventions against valley fever. Our results reveal promising drug-like candidates for drug targets and vaccine targets CID:123631, CID:193962, CID:3045233, CID:6741, CID:214348, CID:11450633 with the identified proteins demonstrating potential efficacy against C posadasii. As we embark on the journey towards translating these discoveries into clinical practice, our findings offer hope for a future where effective treatments for coccidioidomycosis are within reach, promising relief to countless individuals afflicted by this devastating disease.
2026-05-22 | DECTIN-1 stalk length determines binding ability, immune response, and survival in a mouse model of coccidioidomycosis.
Coccidioidomycosis is a leading cause of pneumonia in the endemic area of the Sonora desert and the central valley of California. The causative agent are the fungi Coccidioides immitis and C. posadasii. While most infections ultimately resolve without treatment, some infections spread to the periphery and cause serious and even fatal illness. Much work has shown that a T cell response with production of interleukin-17A and interferon ɣ is critical. Less work has focused on innate responses that ultimately set the stage for the adaptive response. Genetic analysis in both mice and man have shown an important role for DECTIN-1. DECTIN-1 is a C-type lectin receptor that recognizes β-glucans, the main cell wall component of many fungi. Initial recognition through DECTIN-1 modulates fungal binding, host cell uptake, and induces production of a number of cytokines and chemokines. C57BL/6 mice carry a point mutation altering splicing of exon 3, leading to a shorter DECTIN-1 protein lacking a portion of the extracellular stalk. We created mutant C57BL/6 mice to allowing expression of a long-stalk DECTIN-1 consistent with other mouse strains and humans. We directly examined the role of DECTIN-1 stalk length on resistance to infection with the β-glucan-dominant pathogen, C. posadasii. C57BL/6 mice expressing long-stalk DECTIN-1 bound more β-glucan per cell, produced more cytokines, and decreased mortality and dissemination after Coccidioides infection compared with wild-type littermates. The length of the DECTIN-1 stalk controls the outcome of Coccidiodes infection by differential binding and early production of protective cytokines.
2026-02-25 | Use of Epoetin Alfa for Anemia of Chronic Disease in a Jehovah's Witness Teenager With Disseminated Coccidioidomycosis: A Case Report.
Anemia of chronic disease is a common complication of prolonged infection and systemic inflammation and can be difficult to manage in patients who decline blood transfusion, such as Jehovah's Witnesses. Erythropoiesis-stimulating agents are widely used in renal and oncologic settings but are rarely reported in infection-associated anemia among pediatric or young adult patients. We describe a 19-year-old Jehovah's Witness male with disseminated Coccidioides immitis infection complicated by severe anemia of chronic disease. Because blood transfusion was declined, epoetin alfa was administered as a transfusion-sparing strategy prior to surgical intervention. This case highlights a potential role of epoetin alfa as an alternative strategy for managing infection-related anemia in select patients when transfusion is not an option.
2025-09-26 | The Use of Genetics and Immunology in the Diagnosis and Care of Advanced Coccidioidomycosis: Where Are We Going?
Coccidioidomycosis (CM) is an endemic disease in the western United States, northern Mexico, and Central and South America. The severity of coccidioidal infection is highly variable, with potential factors including comorbidities and the patient's innate and adaptive immune response. Based on data from a predominantly healthy and mainly Caucasian male survey conducted nearly a century ago, approximately 60% of infections are asymptomatic, with an estimated 40% of people experiencing some respiratory symptoms; with 10% of those diagnosed with CM. Disseminated disease occurs in approximately 1% of cases and can involve the meninges and, potentially, any place in the body. It is not yet fully understood why some people experience severe disease while many people do not; it is understood that the immune response has a major role. Immunomodulators, including dupilumab and interferon-gamma (IFN-γ), have shown promise in treating patients with disseminated infection. This article summarizes the latest genetic and immunologic evidence demonstrating immune dysfunction. Immunomodulators and potential therapeutic strategies based on the above are reviewed.
2025-05-29 | Interferon-γ Therapy in Patients With Refractory Disseminated Coccidioidomycosis.
Refractory disseminated coccidioidomycosis (DCM) is a severe disease with limited treatment options. This report reviews our own and prior published experiences using adjunctive interferon-γ therapy in refractory DCM, showing overall favorable responses in patients without signal transducer and activator of transcription 1 gain-of-function mutations.
antibodies
2026-09-07 | Coccidioidomycosis in Patients Treated with Dupilumab: A Descriptive Case Series.
A Th2-favored phenotype can predispose individuals to symptomatic and disseminated coccidioidomycosis. Dupilumab, which impedes Th2 immunity, is sometimes used adjunctively for disseminated coccidioidomycosis. To determine whether dupilumab alters the clinical course of coccidioidomycosis, we retrospectively reviewed records of 1,561 patients who received dupilumab; 42 had coccidioidomycosis diagnosed from October 6, 2018, through July 16, 2025 (Mayo Clinic [Phoenix, Arizona]). Eleven patients received dupilumab before having symptomatic coccidioidomycosis, and 3 received dupilumab before asymptomatic coccidioidomycosis was identified. Twenty-eight patients received dupilumab after coccidioidomycosis was diagnosed: 16 were asymptomatic and seropositive, without reactivation on dupilumab, and 12 had ongoing symptoms (most eventually resolved). No patients had adjunctive dupilumab treatment. Three patients had disseminated coccidioidomycosis: 2 initiated dupilumab after coccidioidomycosis was diagnosed and 1 before, and each eventually had symptomatic improvement. We did not observe patterns of coccidioidomycosis worsening after dupilumab initiation or an increased prevalence of coccidioidomycosis among patients already receiving dupilumab.
2026-07-10 | Genetic and transcriptomic determinants of disseminated coccidioidomycosis identify a founder variant in NLRX1 and ancestry-specific rare variants in immune response genes.
Coccidioidomycosis, also known as Valley Fever, is a fungal disease endemic to the Americas that kills hundreds annually, yet the host factors that lead to increased risk of life-threatening dissemination of coccidioidomycosis remain poorly understood. We assembled the largest comprehensively sequenced coccidioidomycosis cohort to date, comprising 795 individuals with laboratory confirmed coccidioidomycosis and clinical disease severity phenotyping, many with paired whole blood genomic and transcriptomic data. Individuals with greater than 50% African genetic ancestry have increased risk for disseminated coccidioidomycosis (DCM) cases (OR=13.37, p=1.08×10-18), reflecting ancestry-associated differences in allele frequencies at immune loci. Transcriptomic profiling (n=267) revealed upregulation of interferon-inducible genes IFI44 and IFI44L, the fungal recognition receptor CLEC4D, and pro-inflammatory protein S100A12, with sex-specific expression differences in immune cell composition. Gene-burden testing identified NOD-like receptor NLRX1 as the only gene carrying significantly more damaging rare variants than expected by chance (p=5.85×10-4). We identified a rare missense variant, NLRX1 p.Arg252Trp (rs145644388), in five patients with DCM that represents a founder variant: all carriers share African local genetic ancestry and carry 0.6-1.1 centimorgans of identical-by-descent sequence, indicating origin from a common ancestor. In gnomAD, NLRX1 p.Arg252Trp shows has higher allele frequency in African (AF=0.00615) compared to European (AF= 2.25×10-5) populations, directly linking this rare variant to population-level African genetic ancestry enrichment in DCM. NLRX1 disruption impairs LC3-associated phagocytosis, an antifungal mechanism in macrophages. Together, these findings reveal both immune gene expression dysregulation and rare-variant architectures associated with African genetic ancestry underlying severe coccidioidomycosis and identify new targets for risk stratification and treatment.
2026-02-12 | Exhausted T cell phenotypes in disseminated coccidioidomycosis.
Coccidioidomycosis presents clinically as a spectrum ranging from self-limiting Uncomplicated Valley Fever (UVF) in most cases to life-threatening Disseminated Coccidioidomycosis (DCM) in rare individuals. A few patterns of immunologic deficits allowing for dissemination have been identified, though the specific defects in most individuals with DCM remain undefined. We hypothesized that chronic antigen exposure in DCM engenders a state of T cell exhaustion. From a cohort of over 300 subjects with confirmed diagnoses of coccidioidomycosis, circulating T cell phenotypes were characterized via flow cytometry and Coccidioides-specific T cell responses were measured using the Activation-Induced Marker (AIM) assay. Male sex was significantly associated with disseminated disease (odds ratio 2.5; 95% CI: 1.5 - 4.0). 52% of subjects showed Coccidioides-specific T cell responses in our AIM assay. We noted a significant difference in subjects sampled in the first year of diagnosis, where only 8% of DCM subjects had T cell responses during this time, as compared to 44% of UVF subjects (p = 0.04). Among DCM patients with detectable AIM responses, CD4+ T cells demonstrated an exhausted phenotype with elevated PD-1 expression compared to UVF subjects. In vitro PD-1 blockade augmented IFNγ production in most tested DCM subjects. These findings suggest that dissemination may occur in some individuals during a period of impaired antigen-specific T-cell activity. Importantly, these responses can be augmented in vitro by PD-1 blocking antibodies, supporting further study of immune checkpoint therapy as an adjunct to antifungal treatment in disseminated coccidioidomycosis.
2025-10-03 | Type-2 immune skewing in patients with disseminated coccidioidomycosis.
Disseminated coccidioidomycosis (DCM) is an often fatal and otherwise intractable condition requiring lifelong antifungal treatment. We have previously shown that a deranged polarization of CD4+ T cells toward a Type-2 phenotype can exist in the context of DCM. Here we studied a large population of subjects to determine the frequency of abnormal Type-2 skewing of CD4+ T cells in patients with coccidioidomycosis and to identify underlying genetic mechanisms supporting this skew. We collected peripheral blood mononuclear cells from 204 patients with coccidioidomycosis, including 96 patients with disseminated disease. We measured immune phenotypes and cytokine production by CD4+ T cells from patients and healthy controls, and comparisons between groups were made based on disease severity and demographics. Whole genome sequencing was conducted on 149 individuals who also had cytokine profiling. We found that ~20% of DCM patients had a CD4+ T-cell compartment that was abnormally skewed toward a Type-2 (IFN-γ-IL-4+) phenotype. Type-2 skewing was highly correlated with male sex, with 80% of moderately skewed (Th2:Th1 ratio > 1.5) and 100% of severely skewed (Th2:Th1 ratio > 2) patients being male. Co-culture of T cells with the IL4R/IL13R-blocking antibody dupilumab rectified their Th1/Th2 skewing. Sequencing revealed rare variants in genes involved in the IL-12-IFN-γ axis in several Type-2 skewed patients, and we validated one such variant in IFNGR1 as hypomorphic. Patients with DCM, especially those who are male, should be screened for Type-2 skewing of CD4+ T cells. Patients with Type-2 skewing should be additionally screened for genetic defects in the IL-12-IFN-γ axis. Our findings give a mechanistic rationale for exploring blockade of IL4R as a treatment option in Type-2 skewed patients with refractory coccidioidomycosis.
2025-04-25 | Immunomodulation in the Treatment of Disseminated Coccidioidomycosis
Introduction Coccidioidomycosis, commonly known as Valley fever, is an endemic fungal infection with a growing impact in the western United States. Patients with disseminated coccidioidomycosis (DCM) represent a rare and life-threatening subset of Valley fever who face years or a lifetime of antifungals to manage their disease. Immunocompromised patients with defective type 1 immunity or excessive type 2 immunity have an increased risk of dissemination. We previously published a single case employing the IL4/IL13 blocker dupilumab as an adjuvant to antifungal therapy. Here we present ten cases of patients in which adjuvant immunomodulation was provided for severe coccidioidomycosis. Methods This is not an interventional trial. Cases were identified at UCLA by infectious disease experts in conjunction with immunology, and all subjects were deemed to be maximally treated with multiple conventional antifungals. Informed consent was obtained. We performed intracellular cytokine staining on CD4+ T cells and measured proportions of interferon gamma (IFN-γ), IL-4, and IL-17A–producing T cells. Treatment with IFN-γ was offered to those subjects showing life-threatening progression of disease despite maximal conventional care. Treatment with dupilumab was offered to those with excessive type-2 skewing. Clinical outcomes were assessed by laboratory studies, imaging results, and mycosis score. Results Our data follow 10 subjects for a median of 6 months after treatment. Our subjects showed excessive type 2-to-1 ratios, mostly due to excessive type 2 immune skewing and less often in subjects with poor type 1 responses. We found reduction of polyclonal type 2 responses in response to treatment with dupilumab. Clinical outcomes in all ten subjects were improved above the baseline state. Conclusions Our work offers a new treatment employing immune modulation by cytokine blockade to treat a life-threatening infectious disease. Patients with poorly controlled disease may benefit from IFN-γ. Furthermore, subjects exhibiting a Th2-skewed response may benefit from dupilumab. Following the Casadevall damage–response framework, this tailored approach aligns immunomodulation with the underlying immunopathology. These observations provide evidence to support proper clinical trials of IFN-γ and dupilumab. Further research is needed to better characterize why cocci disseminates in certain subjects and which patients will benefit from immunomodulation.
small molecules
2026-09-25 | Accelerating research to keep pace with the rising incidence of coccidioidomycosis.
The number of infections caused by the fungal pathogen Coccidioides is rising. In tandem, the number and breadth of researchers studying this important dimorphic fungal pathogen are growing as well. This review focuses on recent advances in the field and identifies areas primed for ongoing rapid growth, with the goal to improve treatments for coccidioidomycosis as soon as reasonably possible. These areas include building genetic tools, high-throughput drug screening, developing immunomodulatory therapies for coccidioidomycosis, and incorporating research methodologies that can be performed outside of the biosafety level 3 laboratory.
2026-07-20 | Olorofim in Treatment of Patients With Poorly Controlled Disseminated Coccidioidomycosis : A Single-Group, Open-Label, Phase 2b, Multicenter Study.
Olorofim, a novel dihydroorotate dehydrogenase inhibitor, may be efficacious in patients with disseminated coccidioidomycosis (DCM) who lack alternative treatment options. To evaluate olorofim effectiveness and adverse events in patients with DCM. Single-group, open-label, phase 2b study. (ClinicalTrials.gov: NCT03583164). Ten U.S. sites. Forty-one patients with DCM and limited or no treatment options. Patients received olorofim alone or in combination with ongoing standard of care during an 84-day main treatment phase. Extended treatment was offered to patients. Mycoses Study Group-European Organization for Research and Treatment of Cancer (MSG-EORTC) criteria for global response based on subcategories of clinical, radiologic, and mycologic response were adjudicated by an independent data review committee (DRC) at days 42 and 84 (main treatment phase). Because the slow pace of serologic improvement in DCM limits global response to stable at best, this article focuses on patient clinical responses. Treatment-emergent adverse events (TEAEs) were compiled for both treatment phases. Forty-one patients with DCM were enrolled from May 2019 to August 2022. Thirty-nine (95.1%) did not have immunosuppression. Central nervous system disease was present in 30 (73.2%) patients, and 13 (43.3%) had a ventriculoperitoneal shunt with or without an Ommaya reservoir. Clinical success as adjudicated by the DRC occurred in 31 of 41 patients (75.6% [95% CI, 59.7% to 87.6%]) at day 42 and 30 of 41 patients (73.2% [CI, 57.1% to 85.8%]) at day 84. The main TEAE was hepatic biochemistry elevation in 9 of 41 patients (21.9%), which was managed by liver enzyme monitoring and dose reduction or pause in 8 patients (19.5%) and drug discontinuation in 1 patient (2.4%). This was a single-group, open-label trial, but a randomized controlled trial would be preferable. Olorofim showed effectiveness in patients with DCM with limited or no therapeutic options. F2G, Ltd.
2026-07-16 | Persenone A from Avocados Exhibits Potent Anti-Fungal Activity against Coccidioides.
Coccidioidomycosis, or Valley fever, is a fungal respiratory disease caused by Coccidioides immitis or Coccidioides posadasii. Clinical manifestations range from asymptomatic infection to chronic pulmonary disease. Despite the increasing endemic range and affected population, therapeutic strategies display moderate efficacy and adverse side effects. This study explores California's rich botanical diversity as a source for agents that inhibit the early stages of Coccidioides development. We established a screening protocol containing a colorimetric metabolism assay and microscopic imaging. We then applied this protocol to extracts derived from local plants in San Diego, California, and discovered a potent inhibitor, persenone A, from avocados.
2026-06-22 | Severe Pulmonary Coccidioidomycosis Treated With Systemic Corticosteroids in an Adolescent Child.
Coccidioidomycosis (CM) is an emerging public health challenge due to an increasing number of cases in the U.S. Diagnosis may be challenging because of its nonspecific presentation, which may lead to treatment delays. In addition, the optimal management of severe pulmonary CM remains unclear. We present the case of an 18-year-old immunocompromised renal transplant recipient with a history of systemic lupus erythematosus who developed acute respiratory distress syndrome (ARDS) secondary to severe pulmonary CM. Following initiation of systemic corticosteroids treatment with standard-of-care antifungals, she demonstrated improved clinical response. Severe pulmonary CM may lead to a significant multiorgan inflammatory response in this infection. Our case explores corticosteroid treatment to downregulate this pathophysiologic process and help facilitate clinical resolution of the critical respiratory symptoms and limit morbidity associated with this infection.
2026-05-28 | Myeloid-derived suppressor cell (MDSC)-like neutrophils induced by pulmonary infection with Coccidioides posadasii exacerbate disease by suppressing CD4+ T cell immunity.
Coccidioidomycosis is a pulmonary disease caused by the dimorphic fungus Coccidioides, which is endemic to the southwestern United States and South America. Coccidioides grows as septate hyphae in soil and forms spores that can become airborne during mechanical disruption of the soil. In the lungs, the inhaled spores develop into large multinucleated spherules, a unique morphology among medically important Coccidioides species, and reproduce by endosporulation. A hallmark of the host immune response toward endosporulating spherules is the robust recruitment and infiltration of Ly6G+ neutrophils. However, the effectiveness of Ly6G+ neutrophils against Coccidioides remains to be studied. Myeloid-derived suppressor cells (MDSCs) are immunosuppressive and share an origin and many phenotypic features with neutrophils. Here, we demonstrated that Ly6G+ cells, but not Ly6C+ cells, increased lung expression of the inhibitory programmed death-ligand 1 (PD-L1) in diseased mice. The Ly6G+PD-L1+ cells share common characteristics of granulocytic MDSCs. Bone-marrow-derived GR-1+ myeloid cells, including both Ly6G+ and Ly6C+ cells, suppressed the proliferation of CD4+ T cells after exposure to spherules. Furthermore, isolated GR-1+ cells from the lungs and spleens of Coccidioides-infected non-protected mice also suppressed CD4+ T cell proliferation, thereby diminishing adaptive T cell responses. Adoptive transfer of GR-1+ myeloid cells isolated from the lungs of Coccidioides-infected mice, or derived from bone marrow exposed to paraformaldehyde-killed spherules, into vaccine-protected recipients exacerbated coccidioidomycosis through the reduction of protective Th1 and Th17 responses. Altogether, we demonstrate that pulmonary infiltration of MDSC-like neutrophils, in non-vaccinated mice, play a detrimental role in coccidioidomycosis by inhibiting protective CD4+ T cell responses. Dimorphic fungi are primary pathogens that infect both immunocompetent and immunocompromised hosts. Fungal pathogens have evolved sophisticated strategies to evade innate immune responses, which have not been well studied. Recently, myeloid-derived suppressor cells (MDSCs) have been described in the pathogenesis of several fungal infections, including Candida albicans and Cryptococcus neoformans. Here, we use a live-attenuated vaccine model to investigate the role of Ly6G+ myeloid cells during Coccidioides infection in mice. We have shown that pulmonary Coccidioides posadasii infection leads to the accumulation of programmed death-ligand 1 (PD-L1)+Ly6G+ MDSC-like neutrophils that suppress CD4+ T cell proliferation and exacerbate disease by reducing protective Th1 and Th17 responses. Moreover, adoptive transfer of GR-1+ myeloid cells isolated from Coccidioides-infected mice into vaccine-protected recipient mice reduced protective efficacy by increasing fungal burden and disease severity. Our data suggest that immunosuppressive Ly6G+PD-L1+ MDSC-like neutrophils play a detrimental role by suppressing protective T cell responses in pulmonary Coccidioides infection.
vaccines
2026-06-25 | Intent to Accept a Valley Fever Vaccine for Humans and Dogs and Factors Influencing Intended Uptake: A Cross-Sectional Survey in Two Endemic Regions.
As Valley fever (coccidioidomycosis) vaccine candidates progress towards human trials, a challenge to their eventual introduction is understanding vaccine demand and addressing vaccine hesitancy. We assessed intent to accept a Valley fever vaccine for humans and dogs in two populations living in highly endemic regions: employees at Kern Medical (KM) in Bakersfield, California (N = 103) and members of the public in West Texas (N = 230). We compared the weighted proportions of each population willing to vaccinate themselves and their dogs by demographic and coccidioidomycosis risk factors and assessed the importance of vaccine-related factors on vaccine uptake in each population. We found that 42% (95% confidence interval (CI): 34-49%) of West Texas residents and 76% (95% CI: 63-85%) of KM employees were willing to accept a coccidioidal vaccine, while 49% (95% CI: 41-58%) of West Texas residents and 74% (95% CI: 58-86%) of KM employees were willing to vaccinate their dogs. Among West Texas residents, vaccination willingness was significantly higher among those with prior awareness of Valley fever (adjusted odds ratio (aOR): 3.83, 95% CI: 1.73, 8.49). Across both study populations, absence of side effects was the most important condition that would increase vaccination willingness. Our results indicate substantial interest in a Valley fever vaccine while suggesting that increased Valley fever awareness and minimal vaccine side effects may be important for increased uptake.
2025-11-17 | Fungal vaccines: so needed, so feasible, and yet so far off.
Invasive fungal infections carry high morbidity and mortality, but there are no fungal vaccines. In this issue of the JCI, Okaa et al. report that endonuclease 2 (Eng2), an antigen shared by the Blastomyces, Histoplasma, and Coccidioides species of fungi, elicits protective immunity in mice against blastomycosis, histoplasmosis, and coccidioidomycosis. These results establish a common antigen that can elicit protection against multiple mycoses, encouraging the development of a pan-fungal vaccine. The road to fungal vaccines is made difficult by the need for effectiveness in immunocompromised individuals, the sporadic nature of fungal disease, and the economics of vaccine development. Despite these hurdles, there is optimism that such vaccines can be developed and perhaps find usefulness as adjuncts to antifungal therapy.
2025-10-08 | Endoglucanase 2 (Eng2), a shared immunodominant antigen in dimorphic fungi that elicits immunity during infection.
We describe here a shared surface and cell wall protein, endoglucanase 2 (Eng2), expressed on the etiological agents that cause the endemic systemic mycoses of North America - Blastomyces, Coccidioides, and Histoplasma. We demonstrate that, despite sequence variation of the protein across these related fungi, exposure to Eng2 vaccinated and protected inbred and humanized HLA-DR4 strains of mice against lethal experimental infections with these fungi by eliciting adaptive immunity mediated by CD4+ T cells. We also show that CD4+ T cell precursors against Eng2 were detectable in naive individuals and that patients who had recovered from these infections evinced a memory and recall CD4+ T cell response to Eng2 and its immunodominant epitopes that we have mapped. We created and cataloged new tools and information, such as immunodominant peptide epitopes of Eng2 from each fungus recognized by inbred mice and humans, and we engineered peptide-MHC II tetramers to track T cells in inbred and HLA-DR4-humanized mice. These tools and tetramers will be useful for those who study these infections in mice and humans. Last, because most patients demonstrated immune memory and recall responses against Eng2, our work offers tools for the diagnosis of this collection of infectious diseases across North America.
2025-06-05 | Recall interferon-γ responses against Coccidioides are a surrogate marker for vaccine response in dogs.
To develop an interferon γ (IFN-γ) recall assay to detect a T-cell response following vaccination because antibody is seldom detected in Δcps1-vaccinated dogs. Peripheral blood mononuclear cells were collected from naturally infected dogs with a history of coccidioidomycosis or dogs from a nonendemic area. Two- to 5-month-old Beagles were vaccinated 2 to 4 times up to 28 days apart with live, avirulent Δcps1 and bled on study days 42, 68, or 90. Peripheral blood mononuclear cells were stimulated with Δcps1 and stained to detect CD4+ T-cell IFN-γ expression. The percentage of CD4+IFN-γ+ T cells compared to unstimulated baseline was calculated for each dog. All 5 naturally infected dogs with coccidioidomycosis had T-cell IFN-γ responses, and the 2 unexposed nonendemic dogs did not. Fourteen of 15 dogs vaccinated with Δcps1 had recall IFN-γ responses. Subcutaneously vaccinated dogs (n = 5) had a mean 1.85-fold increase in IFN-γ over baseline, whereas IM-vaccinated dogs (n = 10) were a mean of 6- to 10-fold higher. The percentage of CD4+IFN-γ+ cells was higher from restimulated cells compared to baseline in both SC- and IM-vaccinated dogs (SC twice [n = 5]: 95% CI, 0.001 to 0.543; IM twice [n = 5]: 95% CI, 0.9734 to 1.948; IM 4 times [n = 5]: 95% CI, 1.207 to 5.083). The T-cell IFN-γ recall assay of peripheral blood mononuclear cells from vaccinated dogs detects a cell-mediated immune response to the Δcps1 vaccine. This assay has potential utility as a surrogate marker for vaccine-induced immunity.
2024-10-04 | From soil to clinic: current advances in understanding Coccidioides and coccidioidomycosis.
SUMMARYCoccidioides immitis and Coccidioides posadasii are fungal pathogens that cause systemic mycoses and are prevalent in arid regions in the Americas. While C. immitis mainly occurs in California and Washington, C. posadasii is widely distributed across North and South America. Both species induce coccidioidomycosis (San Joaquin Valley fever or, more commonly, Valley fever), with reported cases surging in the United States, notably in California and Arizona. Moreover, cases in Argentina, Brazil, and Mexico are on the rise. Climate change and environmental alterations conducive to Coccidioides spp. proliferation have been recently explored. Diagnostic challenges contribute to delayed treatment initiation, compounded by limited therapeutic options. Although antifungal drugs are often effective treatments, some patients do not respond to current therapies, underscoring the urgent need for a vaccine, particularly for vulnerable populations over 60 years old relocating to endemic areas. Despite recent progress, gaps persist in the understanding of Coccidioides ecology, host immune responses, and vaccine development. This review synthesizes recent research advancements in Coccidioides ecology, genomics, and immune responses, emphasizing ongoing efforts to develop a human vaccine.
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2026-03-27 | Immune-Based Prevention and Therapy Against Coccidioidomycosis: Current and Emerging Approaches.
Coccidioidomycosis (CM) is a fungal infection caused by the inhalation of airborne arthroconidia released by Coccidioides spp. Endemic areas include the southwestern United States, Mexico, and parts of South America. The estimated CM cases exceed 300,000 per year. Current treatment for CM is limited and primarily relies on antifungals such as azoles and Amphotericin B. Moreover, concerns about drug cytotoxicity and rising of azole-resistance underscore the need for alternative or adjunctive immune-based prevention and therapies. This review presents recent advances in immune CM intervention and discusses the potential application of emerging antifungal immunotherapy to treat invasive CM. For preventive vaccination, we reviewed the recent development of subunit protein vaccines and mRNA-based vaccines. Prospects for formulating vaccines with potent adjuvants and delivery systems to enhance protective immunity against CM are also provided. For immunotherapy, we reviewed recent reports of antifungal treatment with immunomodulators, CAR-cells and checkpoint inhibitors. Finally, we discuss the application of experimental animal and in vitro models for advancing vaccine and immunotherapeutic development for CM.
2023-08-21 | Application of anti-fungal vaccines as a tool against emerging anti-fungal resistance
After viruses and bacteria, fungal infections remain a serious threat to the survival and well-being of society. The continuous emergence of resistance against commonly used anti-fungal drugs is a serious concern. The eukaryotic nature of fungal cells makes the identification of novel anti-fungal agents slow and difficult. Increasing global temperature and a humid environment conducive to fungal growth may lead to a fungal endemic or a pandemic. The continuous increase in the population of immunocompromised individuals and falling immunity forced pharmaceutical companies to look for alternative strategies for better managing the global fungal burden. Prevention of infectious diseases by vaccines can be the right choice. Recent success and safe application of mRNA-based vaccines can play a crucial role in our quest to overcome anti-fungal resistance. Expressing fungal cell surface proteins in human subjects using mRNA technology may be sufficient to raise immune response to protect against future fungal infection. The success of mRNA-based anti-fungal vaccines will heavily depend on the identification of fungal surface proteins which are highly immunogenic and have no or least side effects in human subjects. The present review discusses why it is essential to look for anti-fungal vaccines and how vaccines, in general, and mRNA-based vaccines, in particular, can be the right choice in tackling the problem of rising anti-fungal resistance.
2019-12-26 | [Dialyzed leukocyte extracts for the treatment of recurrent and severe infections in pediatric patients with cellular immunodeficiency: 15 years of experience].
Dialyzable leukocyte extracts (DLE) have been used to treat several cellular immunodeficiency. To review the experience of a tertiary hospital in the use of DLE for the treatment of recurrent or severe infections in children with acquired cellular immunodeficiency not due to HIV. We reviewed the medical records of all children who received treatment with EDL of human or bovine origin between 1986 and 2000 to detect recurrent or severe infections without response to a specific antimicrobial therapy and with a quantitative or qualitative deficit in the cellular immune response. The dose of DLE was adjusted according to the percentage of T lymphocytes; the evolution of the patient was evaluated retrospectively for 5 years, the immune response was evaluated by subpopulation of lymphocytes and intradermal tests and inhibition of the leukocyte migration assay (LIF) to PPD, coccidioidin, varidase and candidin. 150 children received DLE, age 7.0 ± 5.9 years. The most frequent indications included upper respiratory tract (71%), lower respiratory tract (43%), gastrointestinal tract (15%), urinary tract (15%) and neurological infections (4%) and coccidioidomycosis (3%). After starting the DLE, the numbers of T lymphocytes, LIF to PPD and varidase (> 20%) and the intradermal induration of the test increased (p <0.001). In 6 patients (4%) recurrences of respiratory and gastrointestinal tract infections were observed, which resolved, no adverse effects attributable to the DLE were reported. The use of DLE for recurrent or severe infectious processes in children with cellular immune deficit improved the clinical evolution and the immunological parameters evaluated without adverse effects attributable to their use. Antecedentes: Los extractos dializados de leucocitos (EDL) han sido utilizados en el tratamiento de diversos defectos de la inmunidad celular. Objetivo: Revisar la experiencia en el uso de EDL para tratar infecciones recurrentes o severas en niños con inmunodeficiencia celular adquirida no debida a virus de la inmunodeficiencia oportuna. Métodos: Se revisaron expedientes de niños tratados con EDL humano o bovino entre 1986 y 2000, por infecciones recurrentes o severas sin respuesta a antimicrobianos y con déficit en la respuesta inmune celular. La dosis se ajustó por el porcentaje de poblaciones de linfocitos T. En el seguimiento a cinco años, la respuesta inmune se evaluó por subpoblaciones de linfocitos, intradermorreacción e inhibición de la migración de leucocitos (LIF) a PPD, coccidioidina, varidasa y candidina. Resultados: 150 niños recibieron EDL, edad 7.0 ± 5.9 años. Las indicaciones más frecuentes incluyeron infección respiratoria superior (71 %), respiratoria inferior (43 %), gastrointestinal (15 %), urinaria (15 %), neuroinfección (4 %) y coccidioidomicosis (3 %). Se incrementaron los linfocitos T, el LIF a PPD y varidasa (> 20 %), así como la induración en pruebas de intradermorreacción (p < 0.001). Se resolvieron las infecciones que se presentaron (4 %). No se reportaron efectos adversos. Conclusiones: El uso de EDL mejoró los parámetros inmunológicos y la evolución clínica en niños con déficit inmune celular.
2019-02-20 | Dendritic cell-based immunization induces Coccidioides Ag2/PRA-specific immune response
Valley Fever, or coccidioidomycosis, is caused by a soil-borne, highly virulent fungal pathogen, Coccidioides spp. Infection with Coccidioides can be life-threatening. Since an effective treatment is not available and the T cell-mediated immune response is protective, vaccine development is of interest. In this study, a primary dendritic cell (DC)-vaccine was evaluated for its ability to stimulate Coccidioides antigen-specific immune response in an extremely susceptible BALB/c mouse model. The DC-vaccine (Ag2-DC) was prepared by non-virally transfecting the primary bone marrow-derived DCs with a plasmid DNA encoding Ag2/PRA (protective epitope of Coccidioides). Mice were intranasally immunized with Ag2-DC on days 2 and 10. Immunized mice were necropsied on days 8, 32, and 44. Major organs and blood samples were harvested. The most common indicators of injury (protein, lactate, and albumin), Ag/PRA-specific cytokine-secreting cells, and IgG and its isotypes were determined by biochemical and immunologic assays, respectively. No signs of sickness were noted. Similarly, no significant changes were observed in the levels of total lung protein, lactate, and albumin, in immunized mice compared with healthy control mice. Interferon (IFN-γ), and interleukin (IL)-4 and IL-17 cytokine-secreting cells were observed in lung and lymph nodes upon Ag2-DC immunization. Our results showed that the levels of serum IgG and its isotypes were increased in Ag2-DC-immunized mice. This report provides evidence of DC immunization-stimulated Ag2/PRA-specific immune responses.
2018-05-21 | Helper T‐cell responses and pulmonary fungal infections
Summary The mucosal surface of the respiratory tract encounters microbes, such as fungal particles, with every inhaled breath. When pathogenic fungi breach the physical barrier and innate immune system within the lung to establish an infection, adaptive immunity is engaged, often in the form of helper CD4 T‐cell responses. Type 1 responses, characterized by interferon‐ γ production from CD4 cells, promote clearance of Histoplasma capsulatum and Cryptococcus neoformans infection. Likewise, interleukin‐17A (IL‐17A) production from Th17 cells promotes immunity to Blastomyces dermatitidis and Coccidioides species infection by recruiting neutrophils. In contrast the development of T helper type 2 responses, characterized by IL‐5 production from T cells and eosinophil influx into the lungs, drives allergic bronchopulmonary aspergillosis and poor outcomes during C. neoformans infection. Experimental vaccines against several endemic mycoses, including Histoplasma capsulatum , Coccidioides , Cryptococcus and Blastomyces dermatitidis , induce protective T‐cell responses and foreshadow the development of vaccines against pulmonary fungal infections for use in humans. Additionally, recent work using antifungal T cells as immunotherapy to protect immune‐compromised patients from opportunist fungal infections also shows great promise. This review covers the role of T‐cell responses in driving protection and pathology in response to pulmonary fungal infections, and highlights promising therapeutic applications of antifungal T cells.
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Drug Discovery Landscape
8 orphan drug designations for Coccidioidomycosis, including 1 approved therapy.
8 orphan drug designations for Coccidioidomycosis, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Olorofim | small molecules | EMA | Shionogi B.V. | |
itraconazole | small molecules | FDA | Mayne Pharma International Pty Ltd. c/o Mayne Pharma Inc. | |
olorofim | small molecules | FDA | F2G Limited | |
fosmanogepix | small molecules | FDA | — | Basilea Pharmaceutica Ltd, Allschwil |
selective inhibitor of fungal CYP51 | small molecules | FDA | NQP 1598, Ltd. | |
coccidioidin SD Skin Test Antigen | vaccines | FDA | Approved | Allermed Labortories, Inc. |
Nikkomycin Z | small molecules | FDA | Valley Fever Center for Excellence (1-111 INF) | |
Amphotericin B lipid complex | small molecules | FDA | — | The Liposome Company, Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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