Passive immunization against Cryptococcus neoformans with an isotype-switch family of monoclonal antibodies reactive with cryptococcal polysaccharide

Abstract

The in vivo properties of an immunoglobulin isotype-switch family of monoclonal antibodies specific for the polysaccharide capsule of Cryptococcus neoformans were examined in a murine model of cryptococcosis. Subclass-switch variants were isolated by sequential sublining of an immunoglobulin G subclass 1 (IgGl)secreting cell line. Antibodies of the IgGl, IgG2a, and IgG2b isotypes with identical reactivities with cryptococcal polysaccharide were prepared. The antibodies had the distinct biological properties associated with the heavy chains of each respective isotype. The antibodies were used prophylactically or therapeutically in an attempt to alter the course of cryptococcal infection in mice. Survival of mice and a tissue census of the numbers of viable cryptococci in the lung, spleen, and brain were used as indicators of efficacy. Passive immunization with the IgG2a and IgG2b antibodies effected a reduction in the numbers of cryptococci in lung and spleen. Passive immunization with the IgGl antibody was markedly less effective. Passive immunization had little or no effect on the numbers of cryptococci in brain tissue, regardless of the immunoglobulin isotype. Despite apparent efficacy with regard to reduction in the numbers of yeast cells in the lung and spleen, the results showed no improvement in survival from murine cryptococcosis. Our results indicate that passive immunization produces a modest effect on the course of murine cryptococcosis in tissues other than brain. However, under the experimental conditions used, such treatment does not have a measurable impact on the ultimate outcome of the infection.

Generation of biologically active anti-Cryptococcus neoformans IgG, IgE and IgA isotype switch variant antibodies by acridine orange mutagenesis

“…Anti-C. neoformans antibodies enhance phagocytosis and killing in vitro and confer protection in vivo. Nevertheless, examination of protective efficacy of several MoAbs suggests that both isotype and epitope specificity are very important, with IgG3 demonstrating only marginal protection [8,12,22,23]. The likelihood of recovery of spontaneous isotype switch mutants from hybridoma cell lines is dependent on the frequency of switching events in vitro.…”

Immunotherapy of Cryptococcus infections

“…The protective effect of mAbs in murine models of cryptococcal infection has mostly consisted of prolongation of survival in treated vs. untreated animals [67,69,70,75,79,[82][83][84][85]. Administration of mAbs also has been associated with a reduction of fungal burden in the lungs [70,86], brain [70,71,84], liver [71,87] and spleen [86,87] of treated mice. Prolonged survival in animals treated with mAbs was more frequently associated with downregulation [69,74,75] than with enhancement [82] of the inflammatory response.…”

Utilização de peptídeo sintético (P10) associado ao tratamento com drogas antifúngicas no controle da paracoccidioidomicose experimental

“…(CASADEVALL, 1995). Experimentos com mAb têm demonstrado a existência de anticorpos protetores e não-protetores para C. albicans (HAN e CUTLER, 1995;MATTHEWS et al, 1995) e C. neoformans (DROMER et al, 1987;SANFORD et al, 1990;MUKHERJEE et al, 1992 (MARQUES et al, 2006;TABORDA et al, 1998;TRAVASSOS et al, 1995),…”