Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans.
Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans.
复制标题
新型纳米级噬菌体单域抗体用于治疗白色念珠菌引起的全身感染
DOI：
10.1038/srep32256
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发表时间：
2016-08-25
影响因子：
4.6
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Dong S;Shi H;Cao D;Wang Y;Zhang X;Li Y;Gao X;Wang L
白色念珠菌（C.白色念珠菌）是一种重要的人类共生和机会真菌病原体。分泌型乙酰基蛋白酶（Saps）是C.在这些蛋白酶中，Sap 2的表达水平最高。针对Sap 2的抗体可能提供抗真菌作用。本研究从人源单链抗体库中筛选出两个抗rSap 2单链抗体，并在小鼠C.白色念珠菌通过死亡率、真菌负荷和组织学检查评估体内疗效。相对于对照组，用scFv-EGFP处理后，总体存活率显著增加，而殖民地计数和感染灶显著减少。为了研究由scFv-IFN-γ引起的免疫应答，测量了三种细胞因子（Th 1、Th 2和Th 17型），并观察到明显的免疫应答。这些结果表明，抗rSap 2单链抗体在治疗由C.白色念珠菌
Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans.