Effective resistance to lethal challenge (25 to 100 LD50) with Cryptococcus neoformans has been induced in mice by vaccination with suspensions of formalin-killed cells. A systematic study was made of factors influencing immunization and challenge such as the amount and route of antigen used, the degree of encapsulation of the killed cells, time of challenge and the number of organisms contained in the infecting dose. The importance of the amount of vaccine used was emphasized by the finding of a relatively narrow range between a quantity that evoked effective resistance and a larger quantity that caused a marked reduction in protection. Comparison of vaccines consisting either of small or of large encapsulated cells indicated that large capsule size was associated with decreased protective activity. This finding was observed in tests challenged either with homologous or heterologous cultures.Confirmatory evidence of the effectiveness of immunization was obtained from cultural and histologic examinations of tissues from animals killed at intervals after challenge. Multiplication of cryptococci was largely inhibited in the livers and spleens of vaccinated mice whereas logarithmic rates of growth were observed in the corresponding organs of the controls. The brain examinations showed consistently lower counts of fungus cells in the treated group but the magnitude of the difference, in comparison with the controls, was considerably less than in the other organs that were studied.The implications of some of these findings in relation to the altered course of the infection in vaccinated mice have been discussed.
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