Editorial [Hot Topic: Antifungal Protective Antibodies (Executive Editor: Luciano Polonelli)]

In the last few decades, a plethora of studies have demonstrated the relevance of host acquired immunity against invasive fungal infections. The consolidated consensus that cell-mediated immunity is critical for the successful outcome of fungal infections has been hampered in recent years by the evidence of the role that antibodies may play in host immunoprotection against pathogenic fungi. Today, the major concern is neither the relative importance of cellular and humoral responses nor the modalities of functioning and cooperating of the two arms of the immune system but, rather, the mechanism of action of protective antifungal antibodies. In this issue, the latest and most comprehensive findings on the role played by antibodies in the antifungal defense are reviewed. For Candida albicans, the fungus that has generated the most extensive studies relying on experimental animal models most mimicking human vaginal candidiasis, the potential of passive immunization (i.e. immunotherapy) based on antibodies specific for very characterized virulence factors such as mannans (adhesins), aspartyl-proteinases, other enzymes, germ tube or molecules critical for viability such as heat-shock proteins or cell wall β-glucan is addressed by Antonio Cassone and collaborators. As a matter of fact, the mechanism (deposition of complement factor C3 over the entire yeast cell wall) by which anti-mannan antibodies specific for short chain β-linked oligomannosides as well as a genetically recombinant antibody against fungal heat-shock protein 90 may be protective, alone or in combination with conventional antifungal drugs, against vaginal and disseminated candidiasis is discussed in detail by Jim E. Cutler and Ruth C. Matthews with James P. Burnie respectively. According to an intriguing paradox that existing candidate chemotherapy agents which have recognized potential to increase the risk of fungus infections may represent an excellent resource for the discovery of novel antifungals and targets, the fungicidal and tumoricidal activity of a monoclonal antibody, characterized by a triple anti-C. albicans activity and directed against a proteinic epitope of a cell wall stress mannoprotein recognized to be the major target for secretory IgA, is reported by José Pontón and collaborators. More general insights into the mechanisms of antibody-mediated immunity and the dependance of the cellular response induced by the capsular polysaccharides in the presence or absence of specific protective antibodies are derived from the studies of Arturo Casadevall, Liise-anne Pirofski and Anna Vecchiarelli in Cryptococcus neoformans. The dimorphic fungus Histoplasma capsulatum is, moreover, proffered as a prototype for antibody protection against endemic mycoses by Joshua D. Nosanchuk. Furthermore, the potential of human natural, polyclonal, monoclonal and recombinant yeast killer toxin-like antibodies as well as synthetic killer mimotopes against different pathogenic fungi (including antibiotic-resistant species and strains) is proposed as a wide spectrum antifungal therapeutic approach by Luciano Polonelli's group. Overall, this review summarizes different types of antibodies that can affect the course of yeast and mould infections through interaction with different cellular targets such as mannans, heat shock proteins, capsular polysaccharides, surface proteins, yeast killer toxin receptors which may be envisaged as potential vaccine candidates on their own. The paradigm that the complexity and isotype of protective, non protective and even disease-enhancing antibodies could account for the uncertainty of their role in immunity to fungi and the efficacy of antibodies is dependent on the relative contribution of each of them is now overcome by the technical feasibility and unlimited availability of reproducible human, humanized monoclonal and single chain antibodies as well as genetically engineered antibody fragments of defined specificity which may greatly strengthen the perspectives of antibody-mediated therapy even in individuals with defective immune responses.