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一种新型抗烟曲霉烯醇化酶抗原的单克隆抗体可保护实验性烟曲霉病小鼠。

A novel monoclonal antibody against enolase antigen of Aspergillus fumigatus protects experimental aspergillosis in mice.

机构信息

Division of Microbiology, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow-226031, India.

Academy of Scientific and Innovative Research (AcSIR), Training and Development Complex, CSIR Road, Taramani, Chennai-600113, India.

出版信息

FEMS Microbiol Lett. 2019 Feb 1;366(3). doi: 10.1093/femsle/fnz015.

DOI:10.1093/femsle/fnz015
PMID:30649286
Abstract

Aspergillus fumigatus is one of the most common opportunistic fungal pathogens responsible for a variety of diseases in human, from allergic bronchopulmonary aspergillosis to chronic pulmonary aspergillosis, mostly in immunocompromized patients. In this study, one monoclonal antibody MAb R-5 (IgM) raised against enolase cell surface protein of A. fumigatus exhibited significant inhibition of spore germination in A. fumigatus (88.3%), Aspergillus flavus (57.4%) and Aspergillus niger (30.6%). The MAb R-5 also showed in vitro fungicidal activity against these species as follows: A. fumigatus (24.1%), A. flavus (13.3%) and A. niger (8.8%). These findings were supported by the indirect immunofluorescence microscopy, where the antibody showed binding with germinated spores and hyphae of A. fumigatus as well as A. flavus and A. niger.In vivo protective effect of MAb R-5 was evaluated in BALB/c mice challenged intravenously with A. fumigatus spores, where a significant reduction in CFU (85.9%) was observed in kidney tissue. The mean survival time of mice treated with MAb R-5 (18.5 days) was also enhanced compared to control (6.5 days). These results indicate that MAb R-5 could be valuable in diagnosis as well as in the treatment of broad range of Aspergillus infections.

摘要

烟曲霉是最常见的机会性真菌病原体之一,可导致人类多种疾病,从变应性支气管肺曲霉病到慢性肺曲霉病,主要发生在免疫功能低下的患者中。在这项研究中,一种针对烟曲霉烯醇化酶细胞表面蛋白的单克隆抗体 MAb R-5(IgM)表现出对烟曲霉(88.3%)、黄曲霉(57.4%)和黑曲霉(30.6%)孢子萌发的显著抑制作用。该 MAb R-5 还显示对这些物种的体外杀菌活性如下:烟曲霉(24.1%)、黄曲霉(13.3%)和黑曲霉(8.8%)。间接免疫荧光显微镜检查支持了这些发现,抗体显示与烟曲霉以及黄曲霉和黑曲霉的萌发孢子和菌丝结合。在烟曲霉孢子静脉内攻击 BALB/c 小鼠的体内保护作用评估中,在肾脏组织中观察到 CFU(85.9%)的显著减少。用 MAb R-5 治疗的小鼠的平均存活时间(18.5 天)也比对照(6.5 天)延长。这些结果表明,MAb R-5 可用于广泛的曲霉属感染的诊断和治疗。

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