title: Protection of killer antiidiotypic antibodies against early invasive aspergillosis in a murine model of allogeneic T-cell-depleted bone marrow transplantation.
abstract: Antiidiotypic monoclonal antibodies (MAbs) representing the internal image of a yeast killer toxin (KT) have therapeutic potential against several fungal infections. The efficacy of KT MAbs against Aspergillus fumigatus was investigated in a mouse model of T-cell-depleted allogeneic bone marrow transplantation (BMT) with invasive pulmonary aspergillosis. Mice were highly susceptible to infection at 3 days post-BMT, when profound neutropenia was observed both in the periphery and in the lungs. Treatment with KT MAbs protected the mice from infection, as judged by the long-term survival and decreased pathology associated with inhibition of fungal growth and hyphal development in the lungs. In vitro, similar to polymorphonuclear neutrophils, KT MAbs significantly inhibited the hyphal development and metabolic activity of germinated Aspergillus conidia. These results indicate that mimicking the action of neutrophils could be a strategy through which KT MAbs exert therapeutic efficacy in A. fumigatus infections.
authors.affiliation: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Cenci
authors.forename: Antonella
authors.initials: A
authors.lastname: Mencacci
authors.forename: Antonio
authors.initials: A
authors.lastname: Spreca
authors.forename: Claudia
authors.initials: C
authors.lastname: Montagnoli
authors.forename: Angela
authors.initials: A
authors.lastname: Bacci
authors.forename: Katia
authors.initials: K
authors.lastname: Perruccio
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
authors.forename: Walter
authors.initials: W
authors.lastname: Magliani
authors.forename: Stefania
authors.initials: S
authors.lastname: Conti
authors.forename: Luciano
authors.initials: L
authors.lastname: Polonelli
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001228:Aspergillosis / Q000473:pathology / Q000517:prevention & control*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D005260:Female; D025301:Hyphae / Q000254:growth & development; D008168:Lung / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000473:pathology / Q000517:prevention & control*; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal