State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 430070, China.
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
Dev Comp Immunol. 2021 Feb;115:103906. doi: 10.1016/j.dci.2020.103906. Epub 2020 Oct 28.
Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that caused severe egg drop syndrome in laying ducks in China since 2010, leading to massive economic losses to the duck industry. Although the DTMUV E protein is considered to be critical in inducing the protective immune response, the functional epitopes within this protein remain largely unknown. In the present study, we isolated a DTMUV neutralizing monoclonal antibody (mAb) 3B8 from DTMUV E-immunized mice. Epitope mapping showed that mAb 3B8 recognized a novel linear epitope FSCLGMQNR located on the extreme N-terminal of the domain I (EDI) of E protein. Sequence alignment and Western blot analyses showed that the epitope is greatly conserved with high DTMUV-specificity. Moreover, upon cloning the heavy and light chain variable region sequences of mAb 3B8, we prepared the single-chain variable antibody fragment (scFv) 3B8 by connecting the two chains via a flexible peptide linker. The recombinant scFv 3B8 exhibited antiviral activity against DTMUV infection in vitro and in vivo. Our results provide valuable implications for the development of DTMUV vaccines and therapeutics.
鸭坦布苏病毒(DTMUV)是一种新出现的致病性黄病毒,自 2010 年以来在中国引起产蛋鸭严重的产蛋下降综合征,给养鸭业造成巨大的经济损失。尽管 DTMUV E 蛋白被认为在诱导保护性免疫反应中至关重要,但该蛋白内的功能表位仍知之甚少。本研究从 DTMUV E 免疫的小鼠中分离出一株 DTMUV 中和单克隆抗体(mAb)3B8。表位作图显示,mAb 3B8 识别 E 蛋白结构域 I(EDI)极端 N 端上的一个新的线性表位 FSCLGMQNR。序列比对和 Western blot 分析表明,该表位与 DTMUV 具有高度的保守性和特异性。此外,通过连接两个链的柔性肽接头,我们克隆了 mAb 3B8 的重链和轻链可变区序列,制备了单链可变抗体片段(scFv)3B8。重组 scFv 3B8 表现出体外和体内抗 DTMUV 感染的活性。我们的研究结果为 DTMUV 疫苗和治疗药物的开发提供了有价值的启示。