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确定一种针对葡萄球菌肠毒素B开发的新型人单克隆抗体的免疫特性。

Determining the immunological characteristics of a novel human monoclonal antibody developed against staphylococcal enterotoxin B.

作者信息

Liu Yuanyuan, Song Zhen, Ge Shuang, Zhang Jinyong, Xu Limin, Yang Feng, Lu Dongshui, Luo Ping, Gu Jiang, Zou Quanming, Zeng Hao

机构信息

National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University , Chongqing, PR China.

Clinical Laboratory Department, Army 954th Hospital, General Hospital of Tibet Military Region , Tibet, PR China.

出版信息

Hum Vaccin Immunother. 2020 Jul 2;16(7):1708-1718. doi: 10.1080/21645515.2020.1744362. Epub 2020 Apr 10.

Abstract

Staphylococci are the main cause of nosocomial infections globally. The exotoxin staphylococcal enterotoxin B (SEB) produced by methicillin-resistant is a major cause of pathology after a staphylococcal infection. We previously isolated an anti-SEB human monoclonal antibody designated as M0313. Here we further characterize this antibody in vitro and in vivo. Immunoblotting analysis and ELISA results indicated that M0313 accurately recognized and bound to SEB. Its binding affinity to native SEB was measured at the low nM level. M0313 effectively inhibited SEB from inducing mouse splenic lymphocyte and human peripheral blood mononuclear cell proliferation and cytokine release in cell culture. M0313 also neutralized SEB toxicity in BALB/c female mice. Most importantly, M0313 promoted the survival of mice treated with SEB-expressing bacteria. In-vivo imaging revealed that M0313 treatment significantly reduced the replication of SEB-expressing bacteria in mice. The neutralization capacity of M0313 correlated with its ability to block SEB from binding to major histocompatibility complex II and T-cell receptor by binding to the SEB residues 85-102 and 90-92. Thus, the monoclonal antibody M0313 may be developed into a therapeutic agent.

摘要

葡萄球菌是全球医院感染的主要原因。耐甲氧西林葡萄球菌产生的外毒素葡萄球菌肠毒素B(SEB)是葡萄球菌感染后病理变化的主要原因。我们之前分离出一种抗SEB的人单克隆抗体,命名为M0313。在此,我们进一步在体外和体内对该抗体进行表征。免疫印迹分析和ELISA结果表明,M0313能准确识别并结合SEB。其与天然SEB的结合亲和力在低纳摩尔水平测定。在细胞培养中,M0313有效抑制SEB诱导小鼠脾淋巴细胞和人外周血单个核细胞增殖以及细胞因子释放。M0313还能中和BALB/c雌性小鼠体内的SEB毒性。最重要的是,M0313提高了用表达SEB的细菌处理的小鼠的存活率。体内成像显示,M0313处理显著降低了表达SEB的细菌在小鼠体内的复制。M0313的中和能力与其通过结合SEB的85 - 102位和90 - 92位残基来阻止SEB与主要组织相容性复合体II和T细胞受体结合的能力相关。因此,单克隆抗体M0313有望开发成为一种治疗药物。

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