Fungal Multiplication and Histopathologic Changes in Vaccinated Mice Infected with Coccidioides Immitis

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Abstract
Summary: Multiplication of Coccidioides immitis strain Silveira in the lungs of mice challenged intranasally with arthrospore doses of less than one LD30 was suppressed 50- to 500-fold (at different intervals postchallenge) by vaccination with either intact spherules or isolated spherule walls. At 8 months after challenge with six arthrospores, 74% of the immunized mice and 47% of surviving control mice harbored no organisms in the lungs. At doses of 7 to 15 arthrospores, dissemination to the liver and spleen occurred in 36 to 40% of the control mice but not in immunized mice. The absence of extrapulmonary lesions in vaccinated animals was associated with their augmented capacity to localize the involvement in the lungs; histologic studies showed that pulmonary granulomas in immunized mice had fewer necrotic foci, fewer spherules and more fibrosis than those in control mice. The spherule vaccine of strain Silveira also inhibited the multiplication of an heterologous strain, 46, up to 100,000-fold. In contrast to strain Silveira, many spherules of the relatively avirulent strain 46 were phagocytized by macrophages in granulomas surrounded by dense fibrous connective tissue. The relatively avirulent properties of strain 46 for the mouse appeared to be associated with its susceptibility to phagocytosis rather than with its incapacity to proliferate in vivo.

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