The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations. Antibody genes from Candida-reactive B cell cultures were cloned and expressed in Expi293F human embryonic kidney cells to generate a panel of human recombinant anti-Candida mAbs that demonstrate morphology-specific, high avidity binding to the cell wall. The species-specific and pan-Candida mAbs generated through this technology display favourable properties for diagnostics, strong opsono-phagocytic activity of macrophages in vitro, and protection in a murine model of disseminated candidiasis.

中文翻译：

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单一人类 B 细胞衍生的单克隆抗念珠菌抗体可增强吞噬作用并防止播散性念珠菌病。

全球每年超过一百万的致死性真菌感染的高负担反映了缺乏保护性疫苗、诊断迟缓和化疗不足。在这里，我们通过表达来自念珠菌病患者 B 细胞克隆基因的重组抗体，生成了一组独特的具有诊断和治疗潜力的全人类抗念珠菌单克隆抗体 (mAb)。从抗念珠菌 IgG 血清阳性供体中分离的单类转换记忆 B 细胞在体外进行分化，并针对重组白色念珠菌 Hyr1 细胞壁蛋白和整个真菌细胞壁制剂进行筛选。来自念珠菌反应性 B 细胞培养物的抗体基因被克隆并在 Expi293F 人胚胎肾细胞中表达，以产生一组人重组抗念珠菌单克隆抗体，其表现出形态特异性，与细胞壁结合的高亲和力。通过该技术产生的物种特异性和泛念珠菌单克隆抗体显示出有利的诊断特性、巨噬细胞体外强调理吞噬活性以及在鼠类播散性念珠菌病模型中的保护作用。