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Ebola GP-Specific Monoclonal Antibodies Protect Mice and Guinea Pigs from Lethal Ebola Virus Infection

机译:埃博拉GP特异性单克隆抗体可保护小鼠和豚鼠免受致命的埃博拉病毒感染

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摘要

Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3–4 MAbs to test their protection against a lethal challenge with mouse- or guinea pig-adapted EBOV. Each of the 8 MAbs (100 µg) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3–4 MAbs completely protected the majority of animals, while administration at 2–3 dpi achieved 50–100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection.
机译:埃博拉病毒(EBOV)导致人类和非人类灵长类动物急性出血热,死亡率高达90%。到目前为止,尚无有效的治疗方法。这项研究评估了8种单克隆抗体(MAb)对小鼠和豚鼠的埃博拉糖蛋白的保护作用。免疫适应性小鼠或豚鼠腹膜内注射单克隆抗体。分别以不同剂量或以3–4 MAb的混合物形式使用,以测试其对适应小鼠或豚鼠的EBOV致死性攻击的保护作用。在攻击前或攻击后1天给药时,这8种单克隆抗体(100 µg)均能保护小鼠免受致命性EBOV攻击。感染后2天(dpi)有7个单抗有效,其中1个单抗显示3 dpi的部分保护作用。在豚鼠中,每只单克隆抗体在1 dpi时均表现出部分保护作用,但是与对照组相比,平均死亡时间显着延长。此外,用3–4 MAb的库进行的处理完全保护了大多数动物,而以2–3 dpi的剂量给药可达到50-100%的保护。该数据表明,产生的单克隆抗体能够保护两种动物免受致命的埃博拉病毒攻击。这些结果表明,单克隆抗体,特别是当用作寡克隆化合物时,是用于EBOV感染的暴露后治疗的潜在治疗剂。

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