Developing a vaccine against aspergillosis.

Although there is considerable experimental data to support the idea, bringing a fungal vaccine to fruition has been elusive. Moreover, vaccinating the immunocompromised, susceptible to an opportunistic disease such as invasive aspergillosis, seems formidable. However, pioneering studies using Aspergillus particulate forms or homogenates, and recently, recombinant proteins, have demonstrated feasibility. Moreover, T cell receptors also recognize glycotopes if presented in the appropriate MHC-binding context. The potential role of induced antibody has been appreciated only recently. Recent studies in our laboratory with heat-killed Saccharomyces (HKY) have raised the possibility of development of a panfungal vaccine. This yeast may be nature's experimental reagent, to show the way to a protective protein-carbohydrate conjugate vaccine. Subcutaneous HKY is an effective vaccine against Aspergillus, Coccidioides or Candida challenge. We have learned the protective moiety is in the cell wall, and proteins, glucan and lipid all seem important. We have also found the cell wall glycans alone, mannan or glucan, as a vaccine each provide significant protection. This leads to consideration of the importance of glycosylated proteins and glycan polymer-protein conjugates in vaccine development. We think the most productive route to a fungal-specific vaccine may be a conjugate vaccine that combines the optimally configured glycan with a specific immunogenic protein. Our work so far suggests that some proteins may be sufficiently cross-immunogenic, such that combined with the appropriate glycan, it may be possible to develop a pan-fungal vaccine.