Novel neutralizing monoclonal antibodies against Junin virus

Novel neutralizing monoclonal antibodies against Junin virus
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抗胡宁病毒的新型中和单克隆抗体

DOI:
10.1016/j.antiviral.2018.06.002
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发表时间:
2018-08-01
期刊:
影响因子:
7.6
通讯作者:
Xiao, Gengfu
Xiao, Gengfu
中科院分区:
医学2区
文献类型:
--
作者:
Pan, Xiaoyan;Wu, Yan;Xiao, Gengfu

文献摘要

被引文献

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朱宁病毒(JUNV)是阿根廷出血热的病原体,可导致高致死率,但现有治疗方法有限。本研究通过DNA免疫和抗糖蛋白复合体(GPC)的筛选,获得了一系列的小鼠单抗。最后,发现五种单抗可以有效地中和联合志愿人员方案。进一步的研究表明,它们能够结合构象GPC和负责受体识别的强结合糖蛋白1。表位图谱显示,它们以GP1的环3为靶点,环3中的Tyr122和Asp123是它们的共同结合部位,这可能是它们具有中和活性的原因。这项研究提出了一种新的策略来开发针对JUNV的中和抗体,并为预防JUNV感染提供了治疗候选。
Junin virus (JUNV) is the pathogen of Argentine haemorrhagic fever which results in high lethality, while there is limited therapeutics available. Here, a series of mouse monoclonal antibodies (mAbs) were isolated through immunization with DNA and screening against glycoprotein complex (GPC). Finally, five mAbs were found to effectively neutralize JUNV. Further research indicated that they were capable of binding conformational GPC and strongly binding glycoprotein 1 which is responsible for receptor recognition. Epitope mapping revealed that they targeted loop 3 of GP1, and Tyr122 and Asp123 in loop 3 were identified as their common binding sites, which may account for their neutralizing activity. This study presents a new strategy for developing neutralizing antibodies against JUNV and provides therapeutic candidates for protection against JUNV infection.