Recent progress in vaccines against fungal diseases

Abstract

Diseases caused by fungi are increasingly impacting the health of the human population and now account for a large fraction of infectious disease complications in individuals with impaired immunity or breached tissue defenses. Antifungal therapy is often of limited effectiveness in these patients, resulting into treatment failures, chronic infections and unacceptable rates of mortality, morbidity and their associated costs. Consequently there is a real medical need for new treatments and preventive measures to combat fungal diseases and, toward this goal, safe and efficacious vaccines would constitute major progress. After decades of complacency and neglect of this critically important field of research, remarkable progress has been made in recent years. A number of highly immunogenic and protective vaccine formulations in preclinical setting have been developed, and at least two have undergone Phase 1 clinical trials as preventive and/or therapeutic tools against candidiasis.

Figure 1. Highlights on Th17 cells as a major cellular platform for antifungal defense and vaccination

a) PRR, pattern recognition receptors such as Toll-like receptors, Dectin-1, mannose receptors and others. They can differ between DC and macrophages and be differently involved in recognition of different fungal PAMP (Beta-glucan, mannoproteins, GXM, etc) expressed on fungal surface. b and c) Various mechanisms, often interrelated and involving transcription factors, inflammation activation and cytokines such as type 1-IFN. IL-10, IL-12, IL-23 and others depending on signaling cascade. IL-23 is particularly critical for Th17 expansion d) IL-17 isoforms IL-17 A and IL-17F e) Antifungal defensins, chemokines, inflammatory cytokines, PMN (neutrophils)