Vaccines for human fungal diseases: close but still a long way to go

Despite the substantial global burden of human fungal infections, there are no approved fungal vaccines to protect at risk individuals. Here, we review the progress that has been made and the challenges that lie ahead in the quest towards efficacious fungal vaccines. In mouse studies, protection has been achieved with vaccines directed against fungal pathogens, including species of Candida, Cryptococcus, and Aspergillus, that most commonly cause life-threatening human disease. Encouraging results have been obtained with vaccines composed of live-attenuated and killed fungi, crude extracts, recombinant subunit formulations, and nucleic acid vaccines. Novel adjuvants that instruct the immune system to mount the types of protective responses needed to fight mycotic infections are under development. Candidate vaccines include those that target common antigens expressed on multiple genera of fungi thereby protecting against a broad range of mycoses. Encouragingly, three vaccines have reached human clinical trials. Still, formidable obstacles must be overcome before we will have fungal vaccines licensed for human use.