Anti-β-Glucan Monoclonal Antibody Inhibits Growth and Capsule Formation of Cryptococcus neoformans In Vitro and Exerts Therapeutic, Anticryptococcal Activity In Vivo

• Published in: Infection and Immunity Vol. 75; no. 11; pp. 5085 - 5094
• Main Authors: Rachini, Anna, Pietrella, Donatella, Lupo, Patrizia, Torosantucci, Antonella, Chiani, Paola, Bromuro, Carla, Proietti, Carla, Bistoni, Francesco, Cassone, Antonio, Vecchiarelli, Anna
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.11.2007; American Society for Microbiology (ASM)
• Subjects: Animals; Antibodies, Fungal - immunology; Antibodies, Fungal - therapeutic use; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; beta-Glucans - immunology; Brain - microbiology; Cell Wall - immunology; Cells, Cultured; Colony Count, Microbial; Cryptococcosis - immunology; Cryptococcosis - therapy; Cryptococcus neoformans - growth & development; Cryptococcus neoformans - immunology; Female; Fungal and Parasitic Infections; Glucans; Humans; Immunotherapy; Liver - microbiology; Macrophages - immunology; Mice; Mice, Inbred BALB C; Monocytes - immunology; Phagocytosis; Polysaccharides - immunology; Protein Binding
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00278-07

In this study we tested the in vitro and in vivo anti-Cryptococcus neoformans activity of an antilaminarin (anti-β-glucan) monoclonal antibody (MAb 2G8) (immunoglobulin G2b) which was previously shown to inhibit the growth of β-glucan-exposing Candida albicans cells. Here we show that MAb 2G8 binds to the cell wall of C. neoformans and inhibits its growth to an extent comparable to that observed for C. albicans. Binding and growth inhibition were detected almost equally for encapsulated and acapsular C. neoformans strains. In addition, at subinhibitory concentrations, MAb 2G8 reduced the capsule thickness without affecting protease or phospholipase production. Acapsular fungal cells, but not encapsulated fungal cells, were opsonized by the antibody and more efficiently phagocytosed and killed by human monocytes and by murine peritoneal macrophages. A single administration of MAb 2G8 resulted in a reduction in the fungal burden in the brains and livers of mice systemically infected with a highly virulent, encapsulated C. neoformans strain. This protective effect was also detected in neutropenic mice. Overall, these findings demonstrate that cell wall β-glucan of encapsulated C. neoformans is accessible to antibodies which can exert remarkable anticryptococcal activities in vitro and in vivo.