Role of carbohydrate antigens in antifungal glycoconjugate vaccines and immunotherapy

The emergence of fungal infection is a growing public health concern that in the latest years is becoming a serious threat to humans, particularly for immunocompromised individuals. Invasive fungal infections (IFIs), which are associated with significant morbidity and mortality, are on the rise due to the availability of only a few old antifungal agents. In addition to this, the growing use of antibiotics makes the population increasingly susceptible to these infections. Since carbohydrates are the main component of the fungal cell wall, the study of fungal glycans as potential targets for the fight against IFIs has aroused much interest in recent decades. In most fungal species the saccharides of the core are made up of chitin and β-glucans, while the outer layer carbohydrates vary according to the fungal species, such as mannans for Candida albicans, galactomannans for Aspergillus fumigatus hyphae, α-glucans for Aspergillus fumigatus and Cryptococcus neoformans, glucuronoxylomannans (GXM) and galactoxylomannans (GalXM) for Criptococcus neoformans. Being surface antigens, fungal carbohydrates are a logical target for the development of antifungal glycoconjugate vaccines and for immunotherapy with monoclonal antibodies. This review summarizes recent findings on active and passive immunization strategies based on fungal carbohydrates explored preclinically for three of the major fungal pathogens: Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus.