title: Vaccination with mannan protects mice against systemic aspergillosis.
abstract: Invasive aspergillosis is a major cause of mortality in immunocompromised patients and therapeutic options are often limited, thus a vaccine would be desirable. We presently studied acid-stable cell-wall mannan (α-1, 6-linked backbone highly branched with α-1, 2; α-1, 3; and β-1, 2-linked manno-oligomers) derived from C. albicans, with or without conjugation to bovine serum albumin (BSA), as a vaccine against systemic aspergillosis. Mice were vaccinated subcutaneously with mannan or mannan-BSA conjugate weekly 3 times, ending 2 weeks prior to infection with A. fumigatus conidia. Results showed that the protection induced by mannan is dose-dependent; 12 mg unconjugated mannan alone or > 0.3 mg mannan-BSA consistently enhanced survival (P < 0.05). Fungal burdens in brains and kidneys were reduced after > 0.3 mg of mannan-BSA (all P < 0.05). Mannan-induced protection was improved about 40-fold by conjugation of BSA to mannan. Mannan-BSA (500 kDa) was more protective than 40 kDa mannan-BSA. Mannan is a candidate for a cross-protective conjugate fungal vaccine.
authors.affiliation: California Institute for Medical Research, San Jose, California, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Eva
authors.initials: E
authors.lastname: Machová
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Neščáková
authors.forename: Izabela
authors.initials: I
authors.lastname: Medovarská
authors.forename: Karl V
authors.initials: KV
authors.lastname: Clemons
authors.forename: Marife
authors.initials: M
authors.lastname: Martinez
authors.forename: Vicky
authors.initials: V
authors.lastname: Chen
authors.forename: Slavomir
authors.initials: S
authors.lastname: Bystrický
authors.forename: David A
authors.initials: DA
authors.lastname: Stevens
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000276:immunology / Q000517:prevention & control*; D002176:Candida albicans / Q000737:chemistry / Q000276:immunology; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D008351:Mannans / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D014611:Vaccination / Q000379:methods*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D005657:Fungal Vaccines; D008351:Mannans; D018074:Vaccines, Conjugate