Rev Iberoam Micol. 40 (2023) 1–2 Revista Iberoamericana de Micología www.elsevier.es/reviberoammicol Mycology Forum A promising candidate vaccine for coccidioidomycosis夽 Una prometedora vacuna candidata para la coccidioidomicosis F. Javier Cabañes Veterinary Mycology Group, Department of Animal Health and Anatomy, Veterinary School, Universitat Autònoma de Barcelona, Bellaterra, Spain a r t i c l e i n f o Article history: Received 3 March 2022 Accepted 14 March 2022 Available online 30 June 2022 While we are used to hearing in the media about new and suc- cessful viral vaccine launches, recently in the wake of the COVID-19 pandemic, and we have had a wide range of vaccines against differ- ent bacterial diseases for a long time, there is still not any licensed fungal vaccine for use in humans. This is largely due to the molec- ular complexity of eukaryotic fungal pathogens as immunological targets, together with their ability to evade both naturally acquired and vaccine-induced immunity. However, antifungal resistance is increasing mainly among some species of Aspergillus and Candida, and one strategy to avoid the lack of effectiveness of the antifungal treatments in some mycoses could be the development of fungal vaccines.2 At present, no vaccines against aspergillosis are being developed, and there is little data on the effectiveness of vaccines tested against candidiasis. As far as domestic animals are con- Fig. 1. Characteristic barrel-shaped arthroconidia of Coccidioides species, the infec- cerned, only one fungal vaccine has been successfully licensed so tious spores of the mycelial phase. This 3–5 ␮m arthroconidia are easily dispersed far to reduce clinical signs and prevent ringworm in cattle. This vac- in soil and air and inhaled into the deeper airways of the lungs. Fungal culture cination was introduced in the former Soviet Union in the 1960s by of the mycelial phase carries a high risk of biological contamination. BSL-3 prac- tices, containment equipment, and facilities are recommended for propagating and the Russian mycologist Sarkisov. In this case an attenuated vaccine manipulating sporulating cultures of these species and for processing soil or other containing viable microconidia of Trichophyton verrucosum strain environmental materials known to contain infectious arthroconidia. Lactophenol LTF-130 was used. This strain is still used in the current commercial cotton blue stain. Photo courtesy of Dr. Lisa F. Shubitz. Valley Fever Center for vaccine. Excellence. The University of Arizona. Tucson, USA. Perhaps this lack of vaccines for the prevention of mycoses may soon change with a promising vaccine against coccidioidomyco- sis. To develop this live attenuated vaccine, an avirulent mutant mycosis is common in arid or semi-arid areas, and endemic to the strain of Coccidioides posadasii was previously obtained by delet- Southwestern United States, Mexico, Central America and South ing the CPS1 gene.3 This disease is a systemic mycosis affecting America. Over half of human infections are asymptomatic and con- both animals and humans and is contracted through the inhalation fer disease resistance to future exposure. The rest of the cases suffer of C. posadasii and Coccidioides immitis arthroconidia (Fig. 1). This a clinical disease, estimated to affect approximately 1% of people annually in the highly endemic areas of Arizona and the Central Valley of California. 夽 These Mycology Forum articles can be consulted in Spanish on the Ani- Dogs are also highly susceptible to coccidioidomycosis and have mal Mycology section on the website of the Spanish Mycology Association a higher infection rate than humans. The forms of the disease are (https://aemicol.com/micologia-animal/). similar, but complications in dogs approach 25% of the cases, which E-mail address: javier.cabanes@uab.es often receive long-term treatment with antifungal drugs. The cost https://doi.org/10.1016/j.riam.2022.03.002 1130-1406/© 2022 The Author. Published by Elsevier España, S.L.U. on behalf of Asociación Española de Micologı́a. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). F.J. Cabañes Revista Iberoamericana de Micología 40 (2023) 1–2 of canine coccidioidomycosis, and the affected dogs develop an acute to chronic cough, variable fever, anorexia and weight loss. Dogs with disseminated coccidioidomycosis may have skin lesions, osteomyelitis, central nervous system disease and/or pericardial involvement. Clinical signs of pulmonary or disseminated disease may be present for days to years before dog owners seek veterinary care. With regard to treatment, fluconazole is the main drug used to treat all forms of coccidioidomycosis in dogs, as it is cheaper and has a very high oral bioavailability and relatively low toxicity. Other azoles or amphotericin B are usually selected when the disease does not respond to fluconazole, worsens or spreads. The fungi causing these mycoses are dimorphic. The arthroconi- dia formed in the mycelial phase are inhaled and, thereafter, they turn out within the host tissues into spherules filled with endo- Fig. 2. Cytology of a sample from a dog with coccidioidomycosis showing spherules conidia, the parasitic forms (Fig. 2). Infected small desert-dwelling containing numerous endoconidia. These endoconidia can remain in the lung tissue mammals are the reservoir of Coccidioides species in endemic areas, or disseminate to multiple body sites. Diff-Quik stain. Photo courtesy of Dr. Lisa F. which is a very important fact from the epidemiological point of Shubitz. Valley Fever Center for Excellence. The University of Arizona. Tucson, USA. view of this disease. of these treatments can be an excessive burden to owners, which Conflict of interest may lead to euthanasia or abandonment of the animals. Therefore, the morbidity and mortality of this disease are significant in dogs Author has no conflict of interest. and humans, and an effective vaccine to prevent coccidioidomy- cosis would be beneficial for both. This promising vaccine appears Acknowledgements to be well tolerated in dogs and protects them significantly from experimentally induced coccidioidomycosis. The public per capita Financial support came from Servei Veterinari de Bacteriologia health expenditure related to coccidioidomycosis in the endemic i Micologia of the Universitat Autònoma de Barcelona. regions of the United States is similar to that for polio, measles, mumps or rubella before effective vaccines were available. References In dogs, as well as in human beings, the infection may be asymptomatic or show up as a primary respiratory disease or 1. Davidson AP, Shubitz LF, Alcott CJ, Sykes JE. Selected clinical features of coccid- a disseminated disease.1 However, a high rate of dissemination ioidomycosis in dogs. Med Mycol. 2019;57 Suppl. 1:S67–75. is observed in these animals and may involve almost all tis- 2. Pattison HT, Millar BC, Moore JE. Fungal vaccines. Br J Biomed Sci. 2021;78:167–76. 3. Shubitz LF, Robb EJ, Powell DA, Bowen RA, Bosco-Lauth A, Hartwig A, et al. cps1 sues of the body, with bone being the most common site. As in vaccine protects dogs against experimentally induced coccidioidomycosis. Vac- humans, pulmonary coccidioidomycosis is the most frequent form cine. 2021;39:6894–901. 2