California Institute for Medical Research, San Jose, California, USA.
Med Mycol. 2012 Nov;50(8):818-28. doi: 10.3109/13693786.2012.683539. Epub 2012 May 15.
Invasive aspergillosis is a major cause of mortality in immunocompromised patients and therapeutic options are often limited, thus a vaccine would be desirable. We presently studied acid-stable cell-wall mannan (α-1, 6-linked backbone highly branched with α-1, 2; α-1, 3; and β-1, 2-linked manno-oligomers) derived from C. albicans, with or without conjugation to bovine serum albumin (BSA), as a vaccine against systemic aspergillosis. Mice were vaccinated subcutaneously with mannan or mannan-BSA conjugate weekly 3 times, ending 2 weeks prior to infection with A. fumigatus conidia. Results showed that the protection induced by mannan is dose-dependent; 12 mg unconjugated mannan alone or > 0.3 mg mannan-BSA consistently enhanced survival (P < 0.05). Fungal burdens in brains and kidneys were reduced after > 0.3 mg of mannan-BSA (all P < 0.05). Mannan-induced protection was improved about 40-fold by conjugation of BSA to mannan. Mannan-BSA (500 kDa) was more protective than 40 kDa mannan-BSA. Mannan is a candidate for a cross-protective conjugate fungal vaccine.
侵袭性曲霉病是免疫功能低下患者的主要死亡原因，治疗选择往往有限，因此需要开发疫苗。本研究以白念珠菌来源的酸稳定细胞壁甘露聚糖（α-1,6 连接的主链高度支化，带有α-1,2；α-1,3；和β-1,2 连接的甘露寡糖）为研究对象，研究其作为系统性曲霉病疫苗的潜力，包括与牛血清白蛋白（BSA）偶联和不偶联两种情况。小鼠通过皮下注射每周 3 次甘露聚糖或甘露聚糖-BSA 偶联物进行免疫，在感染烟曲霉孢子前 2 周结束免疫。结果表明，甘露聚糖诱导的保护作用呈剂量依赖性；12mg 未偶联甘露聚糖或>0.3mg 甘露聚糖-BSA 均可显著提高存活率（P<0.05）。>0.3mg 的甘露聚糖-BSA 可降低脑和肾脏中的真菌负荷（均 P<0.05）。BSA 与甘露聚糖偶联可使甘露聚糖诱导的保护作用提高约 40 倍。500kDa 的甘露聚糖-BSA 比 40kDa 的甘露聚糖-BSA 更具保护作用。甘露聚糖是一种具有交叉保护作用的真菌疫苗候选物。
