California Institute for Medical Research, San Jose, CA 95128, USA.
Immunol Invest. 2012;41(8):847-55. doi: 10.3109/08820139.2012.692418. Epub 2012 Jun 11.
We have shown heat-killed Saccharomyces (HKY) is a protective vaccine against aspergillosis and coccidioidomycosis. To test the hypothesis that the efficacy of HKY- induced protection may be due to the cross-reactive antigens in the cell walls of the different fungi, we studied the effect of HKY against systemic candidiasis. Male CD-1 mice were given different regimens of HKY subcutaneously prior to intravenous challenge with Candida albicans. Compared to PBS controls, the administration of HKY (6 × 10(7)) 3, 4 or 6 times prolonged survival (all P < 0.05) and reduced fungal load in the kidney (all P < 0.05). An HKY dose of 1.2 × 10(8) given 4 times prolonged survival (P = 0.02), but showed dose-limiting toxicity. HKY given by an oral route, or by a subcutaneous route with alum as an adjuvant, did not improve survival. Overall, we found that HKY protects mice from infection by Candida albicans in a dose-and regimen-dependent manner. To understand the protection induced by HKY against different fungal species, additional studies of epitope mapping are warranted.
我们已经证明,热灭活的酿酒酵母(HKY)是一种针对曲霉病和球孢子菌病的保护性疫苗。为了验证 HKY 诱导的保护效果可能归因于不同真菌细胞壁中交叉反应抗原的假设,我们研究了 HKY 对系统性念珠菌病的作用。雄性 CD-1 小鼠在静脉内用白色念珠菌攻击前接受不同方案的 HKY 皮下注射。与 PBS 对照组相比,给予 HKY(6×10(7))3、4 或 6 次可延长存活时间(均 P<0.05)并降低肾脏中的真菌负荷(均 P<0.05)。给予 1.2×10(8)剂量的 HKY 4 次可延长存活时间(P=0.02),但表现出剂量限制毒性。通过口服途径或用明矾作为佐剂通过皮下途径给予 HKY 并不能提高存活率。总的来说,我们发现 HKY 以剂量和方案依赖的方式保护小鼠免受白色念珠菌感染。为了了解 HKY 对不同真菌物种诱导的保护作用,需要进一步进行表位作图研究。