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 could induce protection against systemic aspergillosis. CD-1 mice were given three weekly vaccine doses subcutaneously prior to intravenous infection with Aspergillus fumigatus . Mice received PBS, 2.5 mg HKY, whole glucan particles (WGP), WGP conjugated to BSA (0.06 to 12 mg per dose), a soluble medium molecular mass (MMW) β-glucan alone or MMW–BSA (≤24 mg per dose). Survival and c.f.u. were determined, and cytokine induction and anti-β-glucan antibodies were assessed in vaccinated mice. Neither soluble MMW glucan, nor MMW–BSA was effective. HKY protected in two studies (survival and c.f.u. were reduced in brain and kidney organs, P <0.004). Six or 12 mg WGP or WGP–BSA prolonged survival ( P ≤0.004) and reduced c.f.u. in each organ ( P ≤0.015) in both experiments; 0.6 mg WGP or WGP–BSA prolonged survival ( P ≤0.015) and reduced c.f.u. ( 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. upregulation of colony stimulating factors, interferons, TNF-α, chemokines such as MCP-1, MIP-1α, RANTES and KC, and Th17-activating cytokines such as IL-6, IL-1β, IL-17). No anti-β-glucan antibodies were in the sera, suggesting an adaptive T cell-mediated, 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.