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Infection and Immunity, May 2002, p. 2375-2382, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2375-2382.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Protection of Killer Antiidiotypic Antibodies against Early Invasive Aspergillosis in a Murine Model of Allogeneic T-Cell-Depleted Bone Marrow Transplantation

Elio Cenci,1 Antonella Mencacci,1 Antonio Spreca,2 Claudia Montagnoli,1 Angela Bacci,1 Katia Perruccio,3 Andrea Velardi,3 Walter Magliani,4 Stefania Conti,4 Luciano Polonelli,4 and Luigina Romani1*

Microbiology,1 Anatomy Sections, Department of Experimental Medicine and Biochemical Sciences,2 Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia,3 Microbiology Section, Department of Pathology and Laboratory Medicine, University of Parma, Parma, Italy4

Received 2 October 2001/ Returned for modification 19 January 2002/ Accepted 14 February 2002

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.

* Corresponding author. Mailing address: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Phone and fax: 39-075-585-7411. E-mail: lromani{at}unipg.it.

Editor: T. R. Kozel

Infection and Immunity, May 2002, p. 2375-2382, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2375-2382.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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