title: Whole glucan particles as a vaccine against murine aspergillosis.
abstract: 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.
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.|Division of Infectious Diseases, Santa Clara Valley Medical Center, San Jose, CA, USA.|California Institute for Medical Research, San Jose, CA, USA.
authors.forename: Karl V
authors.initials: KV
authors.lastname: Clemons
authors.affiliation: Biothera, Eagan, MN, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Danielson
authors.affiliation: Biothera, Eagan, MN, USA.
authors.forename: Kyle S
authors.initials: KS
authors.lastname: Michel
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.|California Institute for Medical Research, San Jose, CA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Biothera, Eagan, MN, USA.
authors.forename: Nadine C
authors.initials: NC
authors.lastname: Ottoson
authors.affiliation: Biothera, Eagan, MN, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Leonardo
authors.affiliation: California Institute for Medical Research, San Jose, CA, USA.
authors.forename: Marife
authors.initials: M
authors.lastname: Martinez
authors.affiliation: California Institute for Medical Research, San Jose, CA, USA.
authors.forename: Vicky
authors.initials: V
authors.lastname: Chen
authors.affiliation: Biothera, Eagan, MN, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Antonysamy
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.|Division of Infectious Diseases, Santa Clara Valley Medical Center, San Jose, CA, USA.|California Institute for Medical Research, San Jose, CA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Stevens
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D001228:Aspergillosis / Q000276:immunology / Q000517:prevention & control*; D001232:Aspergillus fumigatus / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015169:Colony Count, Microbial; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D005936:Glucans / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D044967:Serum / Q000737:chemistry; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000946:Antigens, Fungal; D016207:Cytokines; D005657:Fungal Vaccines; D005936:Glucans; D018074:Vaccines, Conjugate