Purpose: Despite recent advances in therapy, invasive aspergillosis remains problematic in immunocompromised patient populations making a preventive vaccine desirable. In previous studies, testing a variety of regimens, we showed the efficacy of heat-killed yeasts of Saccharomyces cerevisiae (HKY) in protecting CD-1 mice against systemic aspergillosis. Here we examined protection of additional strains of mice, the species specificity of Saccharomyces as a vaccine, and the inclusion of alum (aluminium hydroxide, which is an immuno-adjuvant). Methods: Male, 5-week-old, CD-1, DBA/2, BALB/c, and C57BL/6 mice were given 6 x 107 HKY (killed at 70Â°C, 3 h) subcutaneously on days 28, 21, and 14, before challenge with (6-9.5) x 106 A. fumigatus conidia. Survival was tallied for 16 d and fungal burdens in brain and kidneys were determined in survivors. To understand whether the protection is HKY-specific, we tested a vaccine derived from Saccharomyces servazzi (Ss-HKY). Results: HKY immunization of BALB/c, DBA/2 and C57BL/6 mice prolonged survival in comparison to their respective controls (P = 0.046, P 0.05). Vaccination of CD-1 mice with HKY plus 20-μg alum adjuvant equalled HKY alone in prolonging survival and was superior in reducing fungal burdens. The brains of all animals receiving HKY plus alum were free of detectable CFU as were the kidneys of 60% of the mice. In comparison, for those given HKY alone only 60% were free of infection in the brain and none in the kidneys. Conclusions: Our study shows that HKY efficacy is not mouse strain specific nor is the efficacy specific only to the species S. cerevisiae. The latter suggests components common in these species are responsible for inducing protection to systemic aspergillosis. In addition, inclusion of alum as an adjuvant with HKY significantly improved outcome. These results are promising for the development of a useful vaccine for prevention of aspergillosis.
Full conference title:
4th Advances Against Aspergillosis
- AAA 4th (2010)