Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection.
Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection.
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DOI：
10.1093/infdis/jiv565
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发表时间：
2016-04-01
期刊：
影响因子：
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通讯作者：
Carroll MW
中科院分区：
文献类型：
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作者：
Dowall SD;Callan J;Zeltina A;Al-Abdulla I;Strecker T;Fehling SK;Krähling V;Bosworth A;Rayner E;Taylor I;Charlton S;Landon J;Cameron I;Hewson R;Nasidi A;Bowden TA;Carroll MW
埃博拉病毒的高度糖基化糖蛋白刺突（EBOV-GP 1，2）是体液宿主应答的主要靶标。用在哺乳动物细胞中表达的重组EBOV-GP胞外域（EBOV-GP 1，2 ecto）免疫绵羊，诱导了强烈的免疫应答，并产生了高滴度的高亲合力多克隆抗体。绵羊抗血清体外中和活性的研究表明，它中和EBOV。从抗血清制备完整的绵羊免疫球蛋白G（本文称为EBOTAb）库，并用于豚鼠体内研究。在激发后6小时给予EBOTAb时，所有动物均存活，未出现发热或其他临床表现。在第二系列豚鼠研究中，EBOTAb给药在激发后延迟48或72小时，分别导致100%和75%的存活。这些研究说明了EBOTAb在预防EBOV引起的疾病方面的有效性。
The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOTAb, was prepared from the antisera and used for an in vivo guinea pig study. When EBOTAb was delivered 6 hours after challenge, all animals survived without experiencing fever or other clinical manifestations. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease.