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A proline rich antigen (PRA), which protects mice against Coccidioides immitis, has been analyzed for differential expression and variation among isolates. Northern blots of RNA from different stages of growth were probed with previously cloned cDNA and showed that mRNA for PRA increased as spherules transformed and matured from mycelia. This pattern corresponds to the relative potency of whole cell vaccines from similar preparations. The PRA gene was then cloned from a genomic library of the Silveira strain of C. immitis and its sequence analyzed. Eight other coccidioidal isolates, selected for diversity in geographic origin and resulting clinical disease, demonstrated heterogeneity in Southern blots and in sequences of polymerase chain reaction products. Silveira differed from other California isolates at 33 of 555 bases, whereas it differed from non-California isolates by <=2 bases. Only one of these substitutions affected protein sequence. Thus, tests or vaccines based on this gene are likely to cover most isolates.
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Cutaneous infection of mice with Candida albicans elicited a predominantly acute inflammatory response, stimulated the production of precipitating antibodies, and conferred protection against subsequent intravenous challenge with the same organism. The acute inflammatory skin reaction seen after cutaneous infection suggested a predominantly humoral response to Candida. Animals infected cutaneously a second time with viable C. albicans developed larger skin lesions than animals infected only once, and the twice-infected animals were more resistant to an intravenous challenge as well. The cutaneous inoculation of mice with heat-killed C. albicans was less effective in stimulating antibody production, in eliciting the inflammatory response, and in inducing a protective response demonstrable by intravenous challenge with viable Candida. This model of experimental candidiasis represents a reproducible means of studying a protective immune response to the organism.
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Galactoglucoxylomannan (GalGXMan) antigen of Cryptococcus laurentii was conjugated to protein carrier by a simple one step reaction. The conjugate was immunogenic in rabbits and reinjection elicited booster response with significant increase of serum IgG (H+L) level. Induction of this Ig-isotype was confirmed in experiments with Protein A. Effectiveness of immune serum to inhibit the growth of C. laurentii was demonstrated. The results indicate that the prepared conjugate could be considered as effective immunogen with potential for incorporation in the vaccine.
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Invasive aspergillosis is a devastating and increasingly common disease, seen almost exclusively in immunosuppressed patients. Immunizing an immunocompromised host would seem to be a formidable task; however, virulence factors and immunogens of the pathogen have now been identified and could be targeted, mapping of the genome sequence of the pathogen will soon be completed, and the protective host immune responses and cytokine networking are better understood. These facts, together with recent advances in vaccine science, make consideration of such an approach now possible. Some populations that are at risk for aspergillosis might be likely candidates for receiving the first vaccinations against aspergillosis, or vaccination of a stem cell donor might be considered in some circumstances. Successful immunizations have been demonstrated in turkeys and mice.
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Three cases of respiratory crytococcosis are described, one diagnosed only after thoracotomy and two after cytology. All were confirmed by cultures, biological and biochemical tests. The patients are alive and well 14 years, 5 years, and 5 years after treatment with crytococcal vaccines and mycostatin. Vaccines proved very effective when given intradermally in small doses and no dangerous reactions were encountered. Cytology of the sputum appears to be a very useful tool in diagnosis of fungal infections of the respiratory tract, especially when supravital staining is used. Difficulties in diagnosis, treatment, and significance of positive sputum findings are discussed.
Five vaccines were prepared from an isolate of Aspergillus fumigatus: a culture filtrate vaccine (I), a spore vaccine (II), a mycelial vaccine (III), and 2 germling vaccines (IV and V). The 2 germling vaccines were produced on different media. Two experiments were conducted to test the vaccines for efficacy in groups of 21 turkey poults by giving each bird 2 subcutaneous inoculations of the respective vaccine at 1 and 2 weeks of age. The birds were challenge exposed to an aerosol of spores of A fumigatus at 1 month of age. The 2 experiments differed only in the challenge exposure. In experiment 1, 38% of the poults were protected when vaccinated with an A fumigatus germling vaccine (IV) and challenge exposed with a dose of aerosolized A fumigatus spores that killed 100% of the nonvaccinated controls. Onset of postchallenge-exposure deaths were delayed by 2 days in the turkeys given vaccine IV. In experiment 2, 48% of the poults were protected when given germling vaccine IV, whereas 62% to 86% of the poults in the nonvaccinated and 3 other vaccine groups died. In experiment 2, 50% of the poults given a mycelial vaccine (III) were protected. Torticollis was a frequent sign of the disease in experiment 2.
A live-trichophyton vaccine against ringworm in cattle which was based on an attenuated strain of Trichophyton verrucosum was tested in controlled challenge-exposure experiments and in field trials. On the basis of data involving approximately 400,000 vaccinated animals over a 5-year period, it was concluded that trichophytosis in cattle can be controlled by immunoprophylaxis. Side effects associated with the vaccination occur infrequently.
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