Immunization of Mice to Coccidioides Immitis: Dose, Regimen and Spherulation Stage of Killed Spherule Vaccines

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Abstract
Summary: Mice immunized intramuscularly with killed spherules of Coccidioides immitis showed an intranasal LD50 > 3000 arthrospores compared to approximately 50 arthrospores in control animals. The immune response was dependent upon factors pertaining to both the host and the vaccine. As early as 7 days postvaccination, the host survived challenge with 85 arthrospores. However, an additional 19 days were required for the induction of immunity to 1000 arthrospores and the development of optimum immunity required more than 30 days. Removal of the footpad vaccination site prior to 30 days impaired the immune response. The extent of the response to intramuscular vaccination was dose-dependent over a 4-fold range and immunity was augmented by administering the vaccine to multiple sites. Injection of baker's yeast resulted in an increased survival of arthrospore-challenged mice but, compared to specific immunization, the protection was slight. The magnitude of the immune response was also influenced by the stage of spherulation. Vaccines prepared from mature spherules were superior to those prepared from immature spherules or endospores. Evidently the spherule walls, previously shown to be the primary locus of the immunogens, increased in immunogenicity concomitantly with maturation of the spherules. Immunity induced by spherules of an old laboratory stock culture and that induced by spherules of a newly isolated strain were comparable in mice challenged intranasally with arthrospores of the homologous or heterologous strains.