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Experimental Murine Cryptococcosis: Effect of Hyperimmunization to Capsular Polysaccharide

Department of Experimental Chemistry, Division of Research, National Jewish Hospital at Denver, Denver, Colorado

Abstract

High levels of humoral antibody directed against cryptococcal capsule are stimulated in mice by immunization with cryptococcal polysaccharide conjugated to bovine -globulin (BGG). Mice so immunized manifest no increased resistance to 75, 5 or even LD₅₀ intravenous challenges with the large capsule homologous organism, and in fact show a slightly enhanced susceptibility to the disease as compared with unimmunized controls. An exploratory immunization with an antigen prepared by decapsulation of cryptococci with dimethylsulfoxide elicited a protective immunity, but only against low level challenge.

Ancillary studies on changes in tissue fungal population with time in infected unimmunized mice, augmented by immunofluorescent examination of sera and tissue homogenates, yielded evidence that a dual natured immune response is stimulated by the infection: production of unprotective humoral anti-polysaccharide and stimulation of an at least partially effective defense mechanism that remains uncharacterized, but which may reside at the cellular level. It is suggested that the "immunologic paralysis" postulated as a consequence of cryptococcal infection is probably relevant only to polysaccharide antigen (soluble or capsular) and as such may have but little influence on active immunity.

Footnotes

This investigation was supported by Public Health Service Research Grant AI-06538 from the National Institutes of Health.

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