Killed Saccharomyces cerevisiae Protects Against Lethal Challenge of Cryptococcus grubii |
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Authors: | Tanya Majumder Min Liu Vicky Chen Marife Martinez Danielle Alvarado Karl V Clemons David A Stevens |
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Institution: | 1. California Institute for Medical Research, 2260 Clove Dr., San Jose, CA, 95128, USA 2. Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, 95128, USA 3. Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, 94305, USA
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Abstract: | Heat-killed Saccharomyces cerevisiae (HKY) vaccination protects mice against aspergillosis, coccidioidomycosis, mucormycosis, or candidiasis. We studied HKY protection against murine cryptococcosis. Once weekly subcutaneous HKY doses (S, 6 × 107; 2S, 1.2 × 108; 3S, 2.4 × 108) began 28 (×3), 35 (×4), or 42 (×6) days prior to intravenous Cryptococcus grubii infection. Survival through 28 days, and CFU in the organs of survivors, were compared to saline-vaccinated controls. In the initial experiment, S, S×4, or 2S reduced brain CFU; liver or spleen CFU was reduced by S×4 or 2S. In a more lethal second experiment, 2S×6, 2S, or 3S×4 improved survival, and HKY regimens reduced CFU in the brain, liver, or spleen, with 2S×6, 2S, or 3S×4 most efficacious. Dose size appears more important than the number of doses: Regimens >S were superior, and 2S and 2S×6 were equivalent. 2S and 3S were equivalent, suggesting doses >2S do not provide additional protection. HKY protects against Cryptococcus, supporting components of HKY as a basis for the development of a panfungal vaccine. |
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