Meningitis due to Cryptococcus neoformans is responsible for upwards of 180,000 deaths worldwide annually, mostly in immunocompromised individuals. Currently there are no licensed
fungal vaccines, and even with anti-fungal
drug treatment,
cryptococcal meningitis is often fatal. Our lab previously demonstrated vaccination with recombinant cryptococcal
proteins delivered in
glucan particles (GPs) protects mice against an otherwise lethal
infection. The aim of the present study was to discover additional cryptococcal
antigens affording
vaccine-mediated protection. Sixteen
proteins, each with evidence of extracellularity, were selected for in vivo testing based on their abundance in protective alkaline extracts of an acapsular C. neoformans strain, their known immunogenicity, and/or their high transcript level during human
infection. Candidate
antigens were recombinantly expressed in E. coli, purified and loaded into GPs. BALB/c and C57BL/6 mice received three
subcutaneous injections of GP-based
vaccine, and survival was assessed for 84 days following a lethal orotracheal challenge with strain KN99. As with our six published GP-
vaccines, we saw differences in overall protection between mouse strains such that BALB/c mice typically demonstrated better survival than C57BL/6 mice. From these studies, we identified seven new
proteins which, when administered as GP-
vaccines, protect BALB/c and/or C57BL/6 mice against cryptococcal
infection. With these results, we expand the pool of novel protective
antigens to eleven
proteins and demonstrate the potential for selection of highly transcribed extracellular
proteins as
vaccine targets. These screens highlight the efficacy of GP-
subunit vaccines and identify promising
antigens for further testing in anti-cryptococcal, multi-
epitope vaccine formulations.