Protection of killer antiidiotypic antibodies against early invasive aspergillosis in a murine model of allogeneic T-cell-depleted bone marrow transplantation.
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.
Cenci
Elio
E
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Mencacci
Antonella
A
Spreca
Antonio
A
Montagnoli
Claudia
C
Bacci
Angela
A
Perruccio
Katia
K
Velardi
Andrea
A
Magliani
Walter
W
Conti
Stefania
S
Polonelli
Luciano
L
Romani
Luigina
L
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
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal