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Original Article

Immunization of mice with induced mutants of Coccidioides immitis

I. Characterization of mutants and preliminary studies of their use as viable vaccines

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Pages 173-184 | Published online: 09 Jul 2009
 

Abstract

Induced auxotrophic mutants of a human isolate of Coccidioides immitis were characterized as to their infection and/or disease causing capacity by intratesticular injection into guinea-pigs and by intranasal instillation into mice. These mutant strains demonstrated degrees of attenuation of virulence to avirulence. Considering this variability in infectivity, 3 of these strains were used as viable vaccines in mice. The results indicate that the individual mutants must produce a primary infection to establish immunity, and that effective immunity can be established which protects against infection up to a certain challenge dosage. Increasing the dosage of the vaccinating strain is given as a means of increasing the immunity of mice.

Other characteristics of these mutants which may be related to their attenuation e.g. their nutritional requirements and growth temperature range, are discussed.

Zusammenfassung

Durch intratestikuläare Injektion beim Meerschweinchen und intranasale Instillation bei der Maus wurde die Infektiosität und Pathogenität von induzierten, auxotrophen Mutanten eines vom Menschen isolierten Stammes von Coccidioides immitis abgeklärt. Die Mutanten zeigten verschiedene Grade von Virulenz bis Avirulenz. Drei Mutanten mit abgeschwächter Virulenz wurden als Lebend-Vakzine bei Mäusen geprüft. Dabei zeigte sich, dass die Mutanten eine Infektion setzen müssen, um immunisierend zu wirken. Je grösser die Mutanten-Dosis, desto ausgeprägter war det Schutz, d.h. desto höhere Infektionsdosen eines normal virulenten Stammes von C. immitis waren erforderlich, um eine Mykose von bestimmter Schwere zu erzeugen.

Bei den Mutanten fanden sich Veränderungen der Kulturbedingungen, z.B. der Nährstoffadsprüche und des Temperaturbereichs; der mögliche Zusammenhang dieser Veränderungen mit der Virulenz-Abschwächung wird diskutiert.

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