# Immune-Based Prevention and Therapy Against Coccidioidomycosis: Current and Emerging Approaches

## TL;DR

This review explores current and emerging immune-based strategies for preventing and treating coccidioidomycosis, a fungal infection.

## Contribution

The paper provides a comprehensive overview of recent advances in immune-based prevention and treatment approaches for coccidioidomycosis.

## Key findings

- Current CM treatment is limited and faces challenges like drug resistance and cytotoxicity.
- Recent developments include subunit protein vaccines, mRNA-based vaccines, and immunomodulators for treatment.
- Animal and in vitro models are key for advancing vaccine and immunotherapy development for CM.

## Abstract

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.