Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody

Abstract

Humoral immunity does not play a prominent role during experimental cryptococcosis. However, previous studies have shown that immunoglobulin G (IgG) anti-Cryptococcus neoformans antibodies can mediate cell-dependent yeast killing in vitro. Therefore, the protective effect of a previously described monoclonal IgG1 anti-C. neoformans antibody (E1) administered intraperitoneally 24 h before intravenous infection with a C. neoformans serotype A strain was evaluated in mice. Heavily infected (3 X 10(6) cells) untreated mice died in 2.9 +/- 0.5 (standard deviation) days. Survival time was 17.9 +/- 1.6 days for mice treated with 100 micrograms of E1 and 3.0 +/- 0.7 days for mice treated with 100 micrograms of a monoclonal IgG1 anti-thyroglobulin antibody used as a control. Protection was dose dependent and required at least 10 micrograms of E1 (mean antibody concentration in serum +/- standard deviation, 6.6 +/- 2.3 micrograms/ml). Insufficient concentrations of IgG anti-C. neoformans antibody could explain previous negative results obtained with polyclonal immune serum. After infection with a smaller inoculum (5 X 10(3) to 5 X 10(4)), the protective effect of E1 was confirmed by the presence of fewer CFUs in the spleens and brains of treated mice than in those of controls. CFU were still detected in the brains of protected mice 5 days after infection, although soluble antigen was negative in sera. These results suggest that passive serotherapy with monoclonal IgG antibodies could participate in the prevention or treatment of experimental cryptococcosis.