Whole Glucan Particles as a Vaccine Against Murine Aspergillosis.

Vaccination with heat-killed Saccharomyces cerevisiae (HKY) protects against experimental infection by pathogenic fungi of five genera. Here we tested whether purified Saccharomyces cell wall β-glucan induced protection against systemic aspergillosis. CD-1 mice were given 3 weekly vaccine doses subcutaneously prior to intravenous infection with Aspergillus fumigatus. Mice received PBS, 2.5 mg HKY, or whole glucan particles (WGP) or WGP conjugated to BSA (0.06 to 12 mg/dose); or a soluble medium molecular weight (MMW) β-glucan alone or MMW-BSA (&le]24 mg/dose). Survival and CFU were determined, and cytokine induction and anti-β-glucan antibodies were assessed in vaccinated mice. Neither soluble MMW glucan, nor MMW-BSA were effective. HKY protected in two studies (survival and CFU reduction brain and kidney, all P < 0.004). WGP or WGP-BSA at 6 or 12 mg prolonged survival (P ≤ 0.004), and reduced CFU in each organ (P ≤ 0.015) in both experiments; the 0.6 mg dose of each prolonged survival (P ≤ 0.015) and reduced CFU (P ≤ 0.015) in one experiment. Cytokine profiles in serum and bronchoalveolar lavage from uninfected vaccinated mice showed an innate and adaptive immune profile (i.e., up-regulation of colony stimulating factors, interferons, TNFα, chemokines such as MCP-1, MIP-1α, RANTES, KC, and Th17- activating cytokines such as IL-6, IL-1β, IL-17). No anti-β-glucan antibodies were in the sera, suggestive of an adaptive T cell, not a B cell mediated protective response. Vaccination with WGP or WGP-BSA proved protective against systemic aspergillosis, equivalent to that of HKY, supporting the potential of particulate β-glucans, alone or conjugated, as vaccines against aspergillosis.