Clemons Karl V, Danielson Michael E, Michel Kyle S, Liu Min, Ottoson Nadine C, Leonardo Steven M, Martinez Marife, Chen Vicky, Antonysamy Mary A, Stevens David A
Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.
Division of Infectious Diseases, Santa Clara Valley Medical Center, San Jose, CA, USA.
J Med Microbiol. 2014 Dec;63(Pt 12):1750-1759. doi: 10.1099/jmm.0.079681-0. Epub 2014 Oct 6.
Vaccination with heat-killed Saccharomyces cerevisiae (HKY) protects against experimental infection by pathogenic fungi of five genera. Here we tested whether purified Saccharomyces cell wall β-glucan could induce protection against systemic aspergillosis. CD-1 mice were given three weekly vaccine doses subcutaneously prior to intravenous infection with Aspergillus fumigatus. Mice received PBS, 2.5 mg HKY, whole glucan particles (WGP), WGP conjugated to BSA (0.06 to 12 mg per dose), a soluble medium molecular mass (MMW) β-glucan alone or MMW-BSA (≤24 mg per dose). Survival and c.f.u. were determined, and cytokine induction and anti-β-glucan antibodies were assessed in vaccinated mice. Neither soluble MMW glucan, nor MMW-BSA was effective. HKY protected in two studies (survival and c.f.u. were reduced in brain and kidney organs, P<0.004). Six or 12 mg WGP or WGP-BSA prolonged survival (P≤0.004) and reduced c.f.u. in each organ (P≤0.015) in both experiments; 0.6 mg WGP or WGP-BSA prolonged survival (P≤0.015) and reduced c.f.u. (P≤0.015) in one experiment. Cytokine profiles in serum and bronchoalveolar lavage from uninfected vaccinated mice showed an innate and adaptive immune profile (i.e. upregulation of colony stimulating factors, interferons, TNF-α, chemokines such as MCP-1, MIP-1α, RANTES and KC, and Th17-activating cytokines such as IL-6, IL-1β, IL-17). No anti-β-glucan antibodies were in the sera, suggesting an adaptive T cell-mediated, not a B cell-mediated, protective response. Vaccination with WGP or WGP-BSA proved protective against systemic aspergillosis, equivalent to that of HKY, supporting the potential of particulate β-glucans, alone or conjugated, as vaccines against aspergillosis.
用热灭活的酿酒酵母（HKY）进行疫苗接种可预防五个属的致病真菌的实验性感染。在此，我们测试了纯化的酿酒酵母细胞壁β-葡聚糖是否能诱导针对系统性曲霉病的保护作用。在经静脉感染烟曲霉之前，给CD-1小鼠每周皮下注射三次疫苗剂量。小鼠接受磷酸盐缓冲盐水（PBS）、2.5毫克HKY、全葡聚糖颗粒（WGP）、与牛血清白蛋白（BSA）偶联的WGP（每剂量0.06至12毫克）、单独的可溶性中分子量（MMW）β-葡聚糖或MMW-BSA（每剂量≤24毫克）。测定存活率和菌落形成单位（c.f.u.），并评估接种疫苗小鼠的细胞因子诱导情况和抗β-葡聚糖抗体。可溶性MMW葡聚糖和MMW-BSA均无效。在两项研究中HKY具有保护作用（脑和肾器官中的存活率和c.f.u.降低，P<0.004）。在两项实验中，6毫克或12毫克WGP或WGP-BSA均可延长存活时间（P≤0.004）并降低各器官中的c.f.u.（P≤0.015）；在一项实验中，0.6毫克WGP或WGP-BSA可延长存活时间（P≤0.015）并降低c.f.u.（P≤0.015）。未感染的接种疫苗小鼠的血清和支气管肺泡灌洗中的细胞因子谱显示出先天性和适应性免疫谱（即集落刺激因子、干扰素、肿瘤坏死因子-α、趋化因子如单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1α、调节激活正常T细胞表达和分泌的趋化因子（RANTES）和KC，以及Th17激活细胞因子如白细胞介素-6、白细胞介素-1β、白细胞介素-17的上调）。血清中未检测到抗β-葡聚糖抗体，这表明是适应性T细胞介导的，而非B细胞介导的保护性反应。用WGP或WGP-BSA进行疫苗接种被证明对系统性曲霉病具有保护作用，与HKY相当，这支持了单独或偶联的颗粒状β-葡聚糖作为抗曲霉病疫苗的潜力。
