Recombinant subunit vaccines against invasive fungal infections: mechanisms, development progress, and therapeutic...

Invasive fungal infections are an escalating global public health threat, especially among immunocompromised populations, with high morbidity and mortality. Traditional antifungal drugs are limited by reduced efficacy, inherent toxicity, and rising drug resistance, creating an urgent need for innovative therapeutic strategies. Recombinant subunit vaccines, as safe, specific, and scalable immunotherapeutics, hold great promise for addressing this unmet medical need. This review systematically summarizes the research advancements of recombinant subunit vaccines against invasive fungal infections. It first elaborates on the immunological mechanisms of fungal infections (innate and adaptive immunity) and the action mechanisms of recombinant subunit vaccines (specific and non-specific immune responses). Then, it categorizes and analyzes vaccines targeting secreted virulence factors, cell wall components, membrane proteins, and post-lysis effector cytoplasmic proteins, detailing their preclinical and clinical development progress. Finally, it discusses core challenges hindering clinical translation, including weak immunogenicity, population heterogeneity, and rapid antigenic evolution, as well as future research directions. Recombinant subunit vaccines have made significant strides from proof-of-concept to late-stage clinical development. Future efforts should focus on optimizing antigen targets, developing novel adjuvants, and addressing population-specific immune disparities to advance the clinical translation of safe, effective, and broad-spectrum antifungal recombinant subunit vaccines.